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    You are here : Home » MS Research News » Stem Cell Research & Treatment » General Stem Cell Research » Adult Stem Cells

    Adult Stem Cells

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    Adult Stem Cells are most commonly "self", meaning they are taken from the person for which they will be used for treatment. The most common source of Adult Stem Cells is a person's Bone Marrow, however, as research procedes it is becoming apparent that other body systems, including blood, adipose tissue(fat) and organs can also be used to produce stem cells for treating an ever increasing number of diseases.

    Mechanism ID’d for benefit of stem cells in autoimmunity

    Stem CellsBone marrow mesenchymal stem cells (BMMSCs) activate a mechanism involving coupling of FAS/FAS ligand to induce T cell apoptosis and immune tolerance, according to an experimental study published online April 26 in Cell Stem Cell.

    To investigate the mechanisms underlying the therapeutic benefit of BMMSCs in autoimmune disease, Kentaro Akiyama, D.D.S., Ph.D., from the University of Southern California in Los Angeles, and colleagues infused BMMSCs into mice.

    The researchers found that, in mice models of systemic sclerosis or experimental colitis, infusion of BMMSCs induced T cell apoptosis via the FAS ligand-dependent FAS pathway, and reduced symptoms of the disease. This was not seen in BMMSCs not expressing the FAS ligand. The apoptotic T cells triggered macrophages to produce transforming growth factor-β which upregulated CD4+CD25+Foxp3+ regulatory T cells leading to immune tolerance. In five patients with systemic sclerosis who received a transplant of allogenic mesenchymal stem cells, disease symptoms improved and the FAS pathway was involved.

    "These data therefore demonstrate a previously unrecognized mechanism underlying BMMSC-based immunotherapy involving coupling via FAS/FAS ligand to induce T cell apoptosis," Akiyama and colleagues conclude.


    Source: Doctors Lounge Copyright © 2001-2012 Doctors Lounge (03/05/12)

    Functional nerve cells generated from adult skin cells

    StemcellsScientists at the University of Connecticut Health Center have successfully converted stem cells derived from the adult skin cells of four humans into region-specific forebrain, midbrain, and spinal cord neurons (nerve cells) with functions. The research is a key step toward realizing the cells’ potential to treat various neurodegenerative diseases.

    The UConn team, led by Dr. Ren-He Xu, director of the Health Center’s Stem Cell Core facility, and Dr. Xuejun Li, a neural scientist in the Neuroscience Department, recently published a paper describing how they used cell reprogramming protocols to first transform the adult tissue into "induced pluripotent stem cells" that are all but identical to embryonic stem cells.

    This involved treating the adult skin cells with a specialized culture that caused them to regress in their development to an embryonic-like “pluripotent” state, capable of differentiating into any of the many tissue types in the body. The researchers then exposed these reprogrammed human cells (hiPSC) to a series of chemical mixtures to drive them into becoming specialized neuronal cells.

    As part of the same research project, Xu’s team also directed two previously established human embryonic stem cell (hESC) lines into neuronal cells, in order to determine whether there were meaningful differences between using human embryonic stem cells and human induced pluripotent cells.

    UConn Health Center scientists who collaborated with Xu and Li on the research included Lixia Yue (a physiologist) and Alexander Lichtler (a geneticist) from the departments of Cell Biology and Regenerative Sciences respectively. Their study was published in PLoS ONE, an international, peer-reviewed online journal of the non-profit Public Library of Science (PLoS).

    The rapid development of iPSCs since they were first produced in 2006 has generated tremendous interest among researchers. The ability to take easily obtainable skin cells and potentially make any tissues in the body eliminates the need to destroy human embryos to obtain hESC. Also, because human iPS cells have the same genetic background as the person they come from, they enable scientists to create perfectly matched cells for patient-specific therapies that would be immune to rejection.

    Yet the research community remains uncertain whether iPS cells have the same quality as hESC. Some biologists suspect that the tissue of origin influences the iPS cells’ ability to develop into different cell lineages; others are not so sure. What they do agree on is that better understanding the mechanisms underlying such epigenetic memory and its consequences is vital to using iPS cells in a clinical setting.

    In their PLoS ONE paper, the UConn researchers contend: “Our results demonstrate that hiPSC, regardless of how they were derived, can differentiate into a spectrum of neurons with functionality, which supports the considerable value of hiPSC for study and treatment of patient-specific neural disorders.”

    Although the differentiation of embryonic stem cells into neuronal cells has been well established in other labs, Li notes that the UConn research is the first to focus on the ability of human iPSC to create functional neurons in region-specific areas of both the brain and spinal cord.

    A key step for using stem cells as therapy in neurological diseases, says Xu, must be developing the ability to direct their differentiation into neural lineages and then to specific neuronal types that are affected by different diseases such as Parkinson’s or Alzheimer’s disease.

    While the UConn study showed that the “efficiency of neural differentiation” among the hiPSC lines was mixed, Xu notes that the process resembled that of the hESC lines in morphology, gene expression, and the chemical signals and conditions needed to regulate how the stem cells programmed to differentiate into neural cells.

    “Together,” he said, “our work has demonstrated that hiPSC, regardless of how they are derived, can generate a spectrum of region-specific neurons.”

    Source: © 2003-2010 (19/10/10)

    Reciprocal Th1 and Th17 regulation by mesenchymal stem cells: Implication for Multiple Sclerosis

    Stem CellsAbstract
    Human mesenchymal stem cells (hMSCs) are being considered for clinical trials of multiple sclerosis (MS).

    We examined the effects of adult bone marrow-derived hMSCs on responses of primary human Th1, Th17, and Th1/17 double-expressing T-cell subsets, all implicated in MS.

    As expected, soluble products from hMSCs inhibited Th1 responses; however, Th17 responses were increased. Secretion of interleukin (IL)-10, considered anti-inflammatory, was decreased.

    Pretreating hMSCs with the proinflammatory cytokine IL-1beta accentuated these effects, and caused decreases in the Th1/17 subset.

    These findings underscore the importance of further preclinical work and immune-monitoring to define hMSC effects on disease-relevant immune responses under variable conditions. ANN NEUROL 2010.

    Darlington PJ, Boivin MN, Renoux C, François M, Galipeau J, Freedman MS, Atkins HL, Cohen JA, Solchaga L, Bar-Or A.

    Neuroimmunology Unit, Montreal Neurological Institute, Quebec, Canada.

    Source: Ann Neurol. 2010 Jul 26 & Pubmed PMID: 20661924

    'Ethical' stem cell crop boosted

    Stem Cells
    US researchers have found a way to dramatically increase the harvest of stem cells from adult tissue.

    It is a practical step forward in techniques to produce large numbers of stem cells without using embryos.

    Using three drug-like chemicals, the team made the procedure 200 times more efficient and twice as fast, the Nature Methods journal reported.

    It is hoped stem cells could one day be widely used to repair damaged tissue in diseases and after injuries.

    Much of the work on stem cells has focused on those taken from embryos as they have an unlimited capacity to become any of the 220 types of cell in the human body - a so-called pluripotent state.

    But this has proven controversial and some campaigners have objected to their use on the grounds that it is unethical to destroy embryos in the name of science.

    The creation of stem cells from human adult skin cells was first reported in 2007 by Japanese and US researchers, opening the way for new sources of stem cells.

    It was done by using viruses to insert four genes into the cells which prompt the switching on and off of other genes and cause the cells to revert to stem cells.

    But the process took weeks and the success rate was only about one in 10,000 cells.

    Better and faster

    The latest research builds on that process by adding specific chemicals to improve the process.

    The Scripps Research Institute team had already boosted the number of cells created with two compounds initiating a naturally occurring process that moves the cell nearer to a stem-cell like state.

    But they have now discovered that by adding thiazovivin, a small molecule involved in cell survival, they doubled that to get 200 times the number of transformed cells.

    The final process also took two weeks compared with a month needed for the original.

    Study leader Professor Sheng Ding said they had manipulated a "fundamental" process in the cell.

    "Both in terms of speed and efficiency, we achieved major improvements over conventional conditions," he said.

    "This is the first example in human cells of how reprogramming speed can be accelerated.

    "I believe that the field will quickly adopt this method, accelerating research significantly."

    Dr Keisuke Kaji, a stem cell researcher at the Medical Research Council Centre for Regenerative Medicine in Edinburgh said the technique was a "great advance" in cell reprogramming technology.

    He added it had already been shown in mouse cells but this was the first time in human cells.

    "I am interested in how widely this drug can have positive effect, for example, if it helps to generate induced pluripotent stem cells from old people's cells which are usually more difficult to reprogram and if it can improve the efficiency in non-viral reprogramming strategies."

    Source: BBC News © British Broadcasting Corporation 2009 (19/10/09)

    Liposuction fat turned into stem cells, study says

    Adipose Stem CellsUsing leftovers from liposuction patients, scientists have turned human fat into stem cells, a new study says.

    The new method is much more efficient than a previous practice that used skin cells, researchers say.

    The discovery may also help avoid the controversy spawned by the use of stem cells from human embryos.

    Human fat is "an abundant natural resource and a renewable one," said Stanford University plastic surgeon Michael Longaker, whose liposuction patients donated the fat for the study.

    Longaker envisions a future in which doctors will be able to use fat from a patient to grow, in a lab, new tissues and organs for that patient.

    The opportunity wouldn't be limited to the obese.

    "Even if you're in great shape, there is still enough fat to be harvested from the vast majority of patients," added Longaker, who co-authored the study.

    From Fat to Stem Cells to New Organs?

    The reprogrammed cells, called induced pluripotent stem cells, or iPS cells, are capable of turning into most types of cells in the body.

    Scientists are keen to obtain these cells to study disease and, one day, use them to grow new tissue and replacement organs.

    Previously, researchers had shown that they could derive this type of stem cell from ordinary skin cells.

    But the fat technique is about twice as fast and 20 times more efficient, said Joseph Wu, the study's senior author.

    "We can get iPS-like colonies, basically, in about 16 days, compared to 28 days to 32 days using [skin]," said Wu, a Stanford stem cell expert. "And if you count the number of colonies in [skin] versus fat ... we get about 20 times more the number of iPS colonies."

    The research appears online in the journal Proceedings of the National Academy of Sciences.

    Reprogramming Cells

    To create the stem cells, the scientists injected Trojan horse-like viruses into smooth muscle cells found in fat that surrounds blood vessels. Once inside, the viruses introduced genes that reprogrammed the cells, spurring them to grow into new forms.

    Previously, this process had required growing the stem cells in a culture dish with nutrients from mouse cells. This had raised alarms about the potential for contamination from mouse proteins—a potential obstacle to government approval, Longaker, the plastic surgeon, said.

    That the new method works at all is "somewhat surprising" and remains something of a mystery, Longaker said.

    Sidestepping Stem Cell Controversy

    The fat and skin methods allow researchers to sidestep the ethical controversy over the use of embryonic stem cells from cell lines originally harvested from unused human embryos from in vitro fertilization clinics.

    In addition, Longaker noted, tissue or organs grown from a patient's own stem cells should be less likely to be rejected by the body.

    The speediness of the fat method, in particular, could be lifesaving, he added.

    For example, if a surgeon wanted to implant new heart tissue—derived from a heart attack victim's own fat—into a patient, the doctor might have only a short time before scar tissue would compromise the operation.

    If he or she were able to generate the tissue within a few weeks, Longaker said, that "would be a big deal."

    Source: National Geographic © 1996-2009 National Geographic Society (09/09/09)

    Discovery of a mechanism controlling the fate of hematopoietic stem cells

    Stem Cells

    Hematopoietic stem cells are capable of manufacturing all types of blood cells. But which factors influence the production of a specific type of cell? Until now, it was thought that this was a random process. At the Centre d'Immunologie de Marseille-Luminy (1), a team of CNRS and Inserm researchers led by Michael Sieweke has discovered the factors that determine the type of cells produced. The mechanism they have demonstrated in the mouse involves one factor intrinsic to the cell and one extrinsic factor.

    These results were published in the journal Cell on July 24, 2009.

    Stem cells are a source of much hope, thanks to their extraordinary ability to produce all types of cell in the body or an organ, depending on their origin.  Scientists are now trying to understand the mechanisms that commit stem cells to a particular specialization.

    At the Centre d'Immunologie de Marseille-Luminy, CNRS and INSERM researchers have been working on mouse hematopoietic stem cells.  They studied the development of myeloid cells, a lineage of white blood cells that combats microorganisms by "eating" them, by releasing toxins or by alerting other specialized immune cells.  Until now, it was thought that the production of different specialised cells from a hematopoietic stem cell was a random process.  Sieweke's team has discovered that in the case of myeloid cells, it is the combined action of two proteins which is relevant; one protein that is situated inside the cell (transcription factor) and the other outside (a cytokine).

    Transcription factors are capable of switching genes on or off.  The identity of a cell is the combination of active genes it possesses.  Because of this, scientists already suspected that transcription factors played an important role in the orientation of differentiation.  They also knew that blood cells can only prosper in an environment containing a particular cytokine, a type of hormone specific to each cell type.  But until now, they thought that cytokines assisted the survival and renewal of cells without affecting their "fate".  The team in Marseille has now shown that a specific cytokine (M-CSF) places stem cells on a "myeloid pathway", but that these stem cells can only follow this path if levels of a certain transcription factor (MafB) within the cells is low.

    These findings help to solve a mystery that has fascinated specialists during the past fifty years.  In the longer term, these results may throw new light on the mechanisms of leukemia, where abnormal stem cells remain "undecided" and are still able to escape therapy.

    Until now, studies on hematopoietic stem cells had opened the way to research on stem cells in other tissues.  In this context, the results achieved and published by Michael Sieweke and his colleagues may provide more general information on how stem cells function (in the brain, muscle or intestine).

    Journal reference:

    1.Sandrine Sarrazin, Noushine Mossadegh-Keller, Taro Fukao, Athar Aziz, Frederic Mourcin, Laurent Vanhille, Louise M. Kelly-Modis, Philippe Kastner, Susan Chan, Estelle Duprez, Claas Otto and Michael H. Sieweke. MAFB Restricts M-CSF Dependent Myeloid Commitment Divisions of Hematopoietic Stem Cells. Cell, 24 July 2009

    Source: Science Daily © 1995-2009 ScienceDaily LLC (31/07/09)

    Boost for safe stem cell treatment

    Stem Cells

    Scientists in Britain and Canada have overcome the biggest obstacle to safe treatments with all-purpose stem cells, created directly from a patient’s own skin.

    The discovery, announced on Sunday night by the journal Nature, is an important step to being able to replace failing tissues anywhere in the human body – while avoiding the ethical problem of creating and destroying human embryos.

    “Combining this work with that of other scientists working on stem cell differentiation, there is hope that the promise of regenerative medicine could soon be met,” said Sir Ian Wilmut, director of the Medical Research Council Centre for Regenerative Medicine at Edinburgh University.

    The new technique eliminates the use of viruses, which would be too risky for patients but had previously been essential for converting adult cells directly into embryonic stem cells.

    Sir Ian’s team worked with Mount Sinai Hospital, Toronto, to find a virus-free way to create “induced pluripotent stem cells” – known as iPS cells – from human skin cells. Human iPS cells, first produced in 2007 by Japanese and US scientists, promise to revolutionise stem cell research. They behave like embryonic stem cells, with the potential to turn into any human tissue, but are created directly from adult cells.

    Until now the main difficulty with making iPS cells has been that the procedure required viruses to carry a package of four genes into the cells. These genes reprogramme the adult cells, taking them back to an embryonic state.

    But viruses are dangerous, mainly because they cause genetic disruption, which could lead to cancer. Labs have been racing to find ways to make iPS cells without using viruses.

    The teams in Edinburgh and Toronto had been working separately on iPS cells, until Andras Nagy from Toronto had a chance meeting with Keisuke Kaji, head of the Edinburgh group. They found that each had independently solved half the problem.

    Dr Kaji discovered how to deliver the four crucial reprogramming genes without using a virus. Dr Nagy was able to remove all trace of the added genes from the new iPS cells, which avoids disrupting the cells’ own genetic machinery.

    The combined approach produced safe iPS cells which behave in laboratory tests just like stem cells taken from embryos. “We hope that these stem cells will form the basis for treatment for many diseases and conditions that are currently considered incurable,” said Dr Nagy.

    The researchers emphasised that much more work was needed before iPS cells could begin clinical trials. “Crucially, we need to have a method to generate the desired cell types from these stem cells,” said Sir Ian.

    Source: The Financial Times Copyright The Financial Times Limited 2009 (02/03/09)

    Stem cell inhibition of Multiple Sclerosis by IDO induction

    Stem Cells

    One of the very interesting things is trying to figure out how stem cells mediate their therapeutic effects in conditions such as multiple sclerosis. In general there are three main ways: 1) Differentiation into neurons/oligodendrocytes; 2) Secrete growth factors; and 3) Immune modulation.

    We are going to discuss a publication (Matysiak et al. Stem cells ameliorate EAE via an indoleamine 2,3-dioxygenase (IDO) mechanism. J Neuro Immunol 2008 Jan;193(1-2):12-23) dealing with immune modulation by stem cells in the mouse model of multiple sclerosis. The mouse model is called experimental allergic encephalomyelitis (EAE). In this paper they induced EAE by immunization with proteolipid protein peptide.

    Mice were injected on day 0. Disease severity increases. Mice recieved 2 million intravenous lineage negative stem cell antigen positive. Subsequent to injection disease severity decreased in the treated group. So the question was whether the stem cells were inducing immune modulation.

    To assess immune modulation the authors evaluated recall response and reported that there was suppressed PLP peptide specific recall response in the mice recieving stem cells. HOWEVER, restimulation of the T cells from mice treated with stem cells resulted in increased interferon gamma production. Interferon gamma is actually associated with inflammation, so this data was very interesting.

    The investigators then sought to see if interferon gamma could be inducing expression of indolamine 2,3 deoxygenase (IDO). This enzyme is associated with suppression of T cells by locally "starving" the T cells of tryptophan. Also IDO is associated with protection of the "fetal allograft" from the maternal immune system.

    The investigators performed Western Blot to assess IDO expression in spleens of stem cell treated and control mice. There was increased basal production of IDO, as well as increase expression in splenocytes of stem cell treated mice subsequent to treatment in vitro with interferon gamma. Additionally, the investigators demonstrated that IDO expression was restricted to the dendritic cell compartment by showing that IDO was found only in the CD11c positive fraction.

    Inhibition of IDO activity by treatment of mice with 1-MT lead to abrogation of the therapeutic effects of stem cell on EAE progress.

    This paper suggests that hematopoietic cells actually induce IDO in dendritic cells as a mechanism of immune regulation. There have been numerous animal models, and early clinical descriptions of stem cells having effects in multiple sclerosis. This paper suggests some possible therapeutic mechanisms.

    Source: © 2006 - 2009 (23/02/09)

    Single virus used to convert adult cells to embryonic stem cell-like cells

    Stem Cells

    Whitehead Institute researchers have greatly simplified the creation of so-called induced pluripotent stem (iPS) cells, cutting the number of viruses used in the reprogramming process from four to one. Scientists hope that these embryonic stem-cell-like cells could eventually be used to treat such ailments as Parkinson's disease and diabetes.

    The earliest reprogramming efforts relied on four separate viruses to transfer genes into the cells' DNA--one virus for each reprogramming gene (Oct4, Sox2, c-Myc and Klf4). Once activated, these genes convert the cells from their adult, differentiated status to an embryonic-like state.

    However, this method poses significant risks for potential use in humans. The viruses used in reprogramming are associated with cancer because they may insert DNA anywhere in a cell's genome, thereby potentially triggering the expression of cancer-causing genes, or oncogenes. For iPS cells to be employed to treat human diseases, researchers must find safe alternatives to reprogramming with such viruses. This latest technique represents a significant advance in the quest to eliminate the potentially harmful viruses.

    Bryce Carey, an MIT graduate student working in the lab of Whitehead Member Rudolf Jaenisch, spearheaded the effort by joining in tandem the four reprogramming genes through the use of bits of DNA that code for polymers known as 2A peptides. Working with others in the lab, he then manufactured a so-called polycistronic virus capable of expressing all four reprogramming genes once it is inserted into the genomes of mature mouse and human cells.

    When the cells' protein-creating machinery reads the tandem genes' DNA, it begins making a protein. However, when it tries to read the 2A peptide DNA that resides between the genes, the machinery momentarily stops, allowing the first gene's protein to be released. The machinery then moves on to the second gene, creates that gene's protein, stalls when reaching another piece of 2A peptide DNA, and releases the second gene's protein. The process continues until the machinery has made the proteins for all four genes.

    Using the tandem genes, Carey created iPS cells containing just a single copy of the polycistronic vector instead of multiple integrations of the viruses. This significant advancement indicates that the approach can become even safer if combined with technologies such as gene targeting, which allows a single transgene to be inserted at defined locations.

    Interestingly, while Carey's single-virus method integrates all four genes into the same location, it has proven to be roughly 100 times less efficient than older approaches to reprogramming. This phenomenon remains under investigation.

    "We were surprised by the lower efficiency," Carey says. "We're not sure why, but we need to look what's going on with expression levels of the polycistronic virus's proteins compared to separate viruses' proteins."

    Although the one virus method is less efficient, Jaenisch maintains it represents an important advance in the field.

    "This is an extremely useful tool for studying the mechanisms of reprogramming," says Jaenisch, who is also a professor of biology at MIT. "Using this one virus creates a single integration in the cells' DNA, which makes things much easier to handle."

    Source: Eureka Alert (16/12/08)

    Stem cell find may alter field

    Stem cells

    A recent breakthrough in stem cell research by seven Harvard affiliates could revolutionize treatment for diseases such as leukemia, for which the only existing cure is bone marrow transplant.

    A new study, released last week in “Nature Biotechnology,” found that some hematopoietic stem cells in bone marrow differentiate more slowly than others.

    According to the study’s principal investigator, Harvard Medical School Professor Hanno R. Hock, such a discovery is “the holy grail of bone marrow transplant therapy.”

    This new study defies the established dogma in the field of stem cell research, which previously assumed that all stem cells divide once every two to four weeks.

    Hock’s research team discovered that 20 percent of stem cells divide less often than expected, only once every 100 days or more.

    Harvard Medical School Professor Vincent J. Carey, a co-author of the study, said he used statistical methods to confirm that “some stem cells are living much longer than anyone expected.”

    These slower-dividing cells constitute a purer population of stem cells—one that could be useful in bone marrow transplant therapy, according to Harvard Medical School research fellow Adlen Foudi, one of the study’s lead co-authors.

    “The less [the cells] divide, the more potent and functional they are,” he said.

    While researchers said they are uncertain about the significance of this new finding, Hock suggested the slower stem cell division could be a biological mechanism to preserve the integrity of the cells. Since genetic mutations accumulate as cells divide, slower division could reduce the rate of mutation, he said.

    The study is a major stride forward in stem cell research, added Hock.

    “These cells are very poorly understood,” according to Hock, who said the surprising results could help develop better clinical applications of stem cell therapy in the future.

    The experiment entailed a novel labeling procedure that allows researchers to examine the rate of stem cell division.

    Hock tagged stem cells with a green marker and then observed that some cells retained a higher label intensity, suggesting that they divided less frequently.

    “We think this [slower division] is the way the body protects the best stem cells,” Hock said.

    However, the new discovery is just the beginning of a new area of research. Foudi said he plans to continue studying these slow-dividing stem cells, the topic of his next paper.

    Source: The Harvard Crimson © 2008, The Harvard Crimson, Inc. (11/12/08)

    Pfizer to open stem cell reseach and development department in Cambridge

    Stem Cell

    Pfizer Inc plans to open a stem-cell research unit in Cambridge. It already operates a similar unit in Cambridge, Mass.

    Researchers hope to use new techniques that give ordinary adults cells the characteristics of embryonic stem cells.

    "These cells will be tremendous in drug discovery," an R&D exec told Reuters. "They will help us understand personalized medicine, genetic variation, ethnic populations, what biomarkers to follow."

    The first uses will be early-stage safety testing. But eventually, work could shift to creating new tissues to be used to treat disease - new heart cells, for example, could repair damaged tissue. Of course, lots of smart people have been trying to figure that sort of thing out for a while now, with very limited success.

    The U.S. depertment will focus on heart disease and diabetes; the U.K. operation will focus on ophthalmology and the central nervous system.

    Source:  SiliconFen Business Report (29/09/08)

    Source of multipotent stem cells with broad regenerative potential identified

    In a promising finding for the field of regenerative medicine, stem cell researchers at Children's Hospital of Pittsburgh of UPMC have identified a source of adult stem cells found on the walls of blood vessels with the unlimited potential to differentiate into human tissues such as bone, cartilage and muscle.

    The scientists, led by Bruno Péault, PhD, deputy director of the Stem Cell Research Center at Children's Hospital, identified cells known as pericytes that are multipotent, meaning they have broad developmental potential. Pericytes are found on the walls of small blood vessels such as capillaries and microvessels throughout the body and have the potential to be extracted and grown into many types of tissues, according to the study.

    "This finding marks the first direct evidence of the source of multipotent adult stem cells known as mesenchymal stem cells. We believe pericytes represent one of the most promising sources of multipotent stem cells that scientists have been searching for in the quest to make regenerative medicine possible," Dr. Péault said. "The encouraging aspect of this source is that blood vessels are the one structure that all tissues in the human body have in common. These cells can be extracted easily and painlessly from convenient sources such as fat tissue, dental pulp, umbilical cord and placental tissue, then grown in culture to large numbers and, possibly, re-injected into the patient to heal a broken bone, a failing joint or an injured muscle."

    In their laboratory in the John G. Rangos Sr. Research Center, researchers were able to identify pericytes in all human tissues they analyzed, including muscle, fat, pancreas, placenta and many other samples. Through purification in the lab, these pericytes could then be coaxed into becoming whatever type of tissue the scientists desired. For instance, the researchers took pericytes from the pancreas and then reinjected them into an injured muscle. The cells immediately began regenerating muscle tissue.

    Results of the study are published in the September issue of the journal Cell Stem Cell.

    Source: ScienceDaily © 1995-2008 ScienceDaily LLC  (23/09/08)

    Scientists produce stem cells for 10 diseases
    Harvard scientists say they have created stems cells for 10 genetic disorders, which will allow researchers to watch the diseases develop in a lab dish.

    This early step, using a new technique, could help speed up efforts to find treatments for some of the most confounding ailments, the scientists said.

    The new work was reported online Thursday in the journal Cell, and the researchers said they plan to make the cell lines readily available to other scientists.

    Dr. George Daley and his colleagues at the Harvard Stem Cell Institute used ordinary skin cells and bone marrow from people with a variety of diseases, including Parkinson's, Huntington's and Down syndrome to produce the stem cells.

    The new cells will allow researchers to "watch the disease progress in a dish, that is, to watch what goes right or wrong," Doug Melton, co-director of the institute, said during a teleconference.

    "I think we'll see in years ahead that this opens the door to a new way to treating degenerative diseases," he said.

    The new technique reprograms cells, giving them the chameleon-like qualities of embryonic stem cells, which can morph into all kinds of tissue, such as heart, nerve and brain. As with embryonic stem cells, the hope is to speed medical research.

    Research teams in Wisconsin and Japan were the first to report last November that they had reprogrammed skin cells, and that the cells had behaved like stem cells in a series of lab tests. Just last week, another Harvard team of scientists said they reprogrammed skin cells from two elderly patients with ALS, or Lou Gehrig's disease, and grew them into nerve cells.

    Melton said the new disease-specific cell lines "represent a collection of degenerative diseases for which there are no good treatments and, more importantly, no good animal models for the most part in studying them."

    A new laboratory has been created to serve as a repository for the cells, and to distribute them to other scientists researching the diseases, Melton said.

    "The hope is that this will accelerate research and it will create a climate of openness," said Daley.

    He expects stem cell lines to be developed for many more diseases, noting, "this is just the first wave of diseases." Other diseases for which they created stem cells are Type 1, or juvenile, diabetes; two types of muscular dystrophy, Gaucher disease and a rare genetic disorder known as the "bubble boy disease."

    Daley stressed that the reprogrammed cells won't eliminate the need or value of studying embryonic stem cells.

    "At least for the foreseeable future, and I would argue forever, they are going to be extremely valuable tools," he said.

    The reprogramming work was funded by the National Institutes of Health and private contributions to the Harvard Stem Cell Institute.

    Source: The Associated Press © 2008 The Associated Press (08/08/08)

    Adult stem cells reprogrammed in the brain, hopes for diseases such as Multiple Sclerosis
    In recent years, stem cell researchers have become very adept at manipulating the fate of adult stem cells cultured in the lab. Now, researchers at the Salk Institute for Biological Studies achieved the same feat with adult neural stem cells still in place in the brain.

    They successfully coaxed mouse brain stem cells bound to join the neuronal network to differentiate into support cells instead.

    The discovery, which is published ahead of print on Nature Neuroscience's website, not only attests to the versatility of neural stem cells but also opens up new directions for the treatment of neurological diseases, such as multiple sclerosis, stroke and epilepsy that not only affect neuronal cells but also disrupt the functioning of glial support cells.

    "We have known that the birth and death of adult stem cells in the brain could be influenced be experience, but we were surprised that a single gene could change the fate of stem cells in the brain," says the study's lead author, Fred H. Gage, Ph.D., a professor in the Laboratory for Genetics and the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Diseases.

    Throughout life, adult neural stem cells generate new brain cells in two small areas of mammalian brains: the olfactory bulb, which processes odors, and the dentate gyrus, the central part of the hippocampus, which is involved in the formation of memories and learning.

    After these stem cells divide, their progenitors have to choose between several options remaining a stem cell, turning into a nerve cell, also called a neuron, or becoming part of the brain's support network, which includes astrocytes and oligodendrocytes.

    Astrocytes are star-shaped glia cells that hold neurons in place, nourish them, and digest parts of dead neurons. Oligodendrocytes are specialized cells that wrap tightly around axons, the long, hair-like extensions of nerve cell that carry messages from one neuron to the next. They form a fatty insulation layer, known as myelin, whose job it is to speed up electrical signals traveling along axons.

    When pampered and cosseted in a petri dish, adult neural stem cells can be nudged to differentiate into any kind of brain cell but within their natural environment in the brain career options of neural stem cells are thought to be mostly limited to neurons.

    "When we grow stem cells in the lab, we add lots of growth factors resulting in artificial conditions, which might not tell us a lot about the in vivo situation," explains first author Sebastian Jessberger, M.D., formerly a post-doctoral researcher in Gage's lab and now an assistant professor at the Institute of Cell Biology at the Swiss Federal Institute of Technology in Zurich. "As a result we don't know much about the actual plasticity of neural stem cells within their adult brain niche."

    To test whether stem cells in their adult brain environment can still veer off the beaten path and change their fate, Jessberger used retroviruses to genetically manipulate neural stem cells and their progeny in the dentate gyrus of laboratory mice. Under normal conditions, the majority of newborn cells differentiated into neurons. When he introduced the Ascl1, which had previously been shown to be involved in the generation of oligodendrocytes and inhibitory neurons, he successfully redirected the fate of newborn cells from a neuronal to an oligodendrocytic lineage.

    "It was quite surprising that stem cells in the adult brain maintain their fate plasticity and that a single gene was enough to reprogram these cells," says Jessberger. "We can now potentially tailor the fate of stem cells to treat certain conditions such as multiple sclerosis."

    In patients with multiple sclerosis, the immune system attacks oligodendrocytes, which leads to the thinning of the myelin layer affecting the neurons' ability to efficiently conduct electrical signals. Being able to direct neural stem cells to differentiate into oligodendrocytes may alleviate the symptoms.

    Source: Huliq News © 2008 (01/07/08)

    Researchers test egg-free stem cells
    A group of Melbourne researchers has become the first in Australia to test the effectiveness of egg-free human embryonic stem cells.

    Induced pluripotent stem cells (IPS), are made by reprogramming adult cells to be more like embryonic cells.

    Still in the research stage, scientists believe IPS cells could be the cure for a range of conditions, without the controversy of embryo-derived stem cells.

    It is the first time the cells have been tested outside of the United States and Japan.

    The Australian Stem Cell Centre at Monash University imported the adult cells from the United States.

    Researcher, Dr Andrew Laslett says he hopes the new stem cells can one day be used to produce human blood.

    "The reason why we're so interested in these cells, is that these cells have the capacity to turn into any cell type in the human body, which you might recall is very similar to the properties of human embryonic stem cells," he said.

    "We would hope that maybe they would be able to be used in sort of an off the shelf product, having been turned into different cells in the body, that could be used to treat people in a hospital setting."

    Source: ABC News © 2008 ABC (10/06/08)

    New Venture For Therapy With Cord Blood And Adult Stem Cells

    Professor Colin McGuckin, Chair in regenerative medicine at Newcastle University and the Fondation Jérôme Lejeune in Paris have announced the formation of a new venture 'Novussanguis ' to promote responsible research on cord blood and adult stem cells. Some 200 international participants were invited to the launch of the consortium at the Medical School of University Paris Descartes, in France.

    Novussanguis will try to help those patients who could benefit from treatment with adult and cord blood stem cells. Adult stem cells can be harvested from several human tissues such as brain, bone marrow, peripheral blood, liver, cornea, retina, pancreatic cells and umbilical cord blood. With over 130 million births per year world-wide, cord blood is a particularly important source of readily available stem cells because of ease of access and supply. Stem cells play a key role in research for treatment of several diseases. Today, over 80 diseases can be treatable with cord blood stem cells. Most of these are linked to the blood system (e.g. leukaemia) or the immune system ('babies in a bubble'), but are also applicable to diseases affecting the bone marrow, nervous system, heart or metabolism such as juvenile diabetes.

    The processing of cord blood and cells involves using high specification machines and technology in the laboratory. Prof. McGuckin's laboratory at Newcastle, England are Planer users and many other clinical and research laboratories around the world use the special freezers from the London based company. Controlled rate freezers are used to pre cool valuable samples before storage in ultra cold liquid nitrogen - so that when thawed the viability of the cells is optimum.

    The Novussanguis consortium is a platform of researchers - initially consisting of fifteen laboratories. The first projects to be financed by Novussanguis will carry out research on nervous tissues damaged by strokes; pancreatic tissues that can produce insulin in vitro for diabetes research; cardiac tissues damaged by a myocardial infarction; epithelial tissues to improve treatment of wound healing; cornea, nervous tissues, bone, cartilage, tendons and blood vessels for orthopaedic applications; epigenetic profiling of cord blood stem cells to improve tissue engineering; expansion and clinical cryo-preservation of cord blood stem cells.

    By using this shared network of knowledge Novussanguis hopes to accelerate advancements in stem cell research. The information gained can then filter down through its network and be used to maximum effect wherever possible.

    Source: Medical News Today © 2008 MediLexicon International Ltd (12/05/08)

    Stem cell hope for paralysed

    Paralysed people could gain the use of their limbs again after scientists found a 'messaging system' that could be used to control adult stem cells.

    Researchers found the cells respond to chemical signals which instruct them to help repair tissue.

    The work, funded by the Medical Research Council, could eventually lead to the development of techniques to tell adult stem cells to mend the body.

    Scientists at the University of Manchester made the discovery while studying mesenchymal stem cells found in human bone marrow.

    These have the ability to relocate and develop into several types of cells and tissue.

    Receptors on the surface of MSCs receive messages in the form of molecules called growth factors that are involved in directing human growth and development.

    A complex system relays and co-ordnates the signals from growth factors to the MSCs, encouraging their development into new blood vessels.

    Prof Cay Kielty, of the University of Manchester, said: 'What we have shown is that adult stem cells respond in particular ways to some of the chemical signals in the body.'

    The scientists are now keen to learn how adult stem cells can be controlled, based on signalling systems that normally give instructions in the body.

    Prof Kielty said: 'The next stage will be to understand how this messaging system regulates relocation of the MSCs and tells them to become blood vessel cells.

    'After that, we can look at applying our understanding to develop stem-cell derived therapies for tissue repair.'

    Source: Top of page ©2008 Associated Newspapers Limited (11/04/08)

    Stem cells made to mimic disease
    Scientists have taken skin cells from patients with eight different diseases and turned them into stem cells.

    The advance means scientists are moving closer to using stem cells from the patient themselves to treat disease.

    This would mean they could circumvent the ethical and practical problems of using embryonic stem cells, which has sparked much opposition.

    Researcher Dr Willy Lensch, of Harvard Medical School, said the technique had "incredible potential".

    He said it could help scientists understand the earliest stages of human genetic disease.

    The stem cells were created by taking biopsies from patients with diseases such as Huntington's and muscular dystrophy.

    However, scientists admit that many risks remain and therapies could still be well over a decade away.

    Induced pluripotent stem (IPS) cells are adult stem cells which are made to act like embryonic ones - they gain the ability to become any cell in the human body.

    But crucially, scientists do not have to destroy embryos to create a supply.

    In principle, they could then be used to treat a wide range of disorders, from diabetes to Parkinson's.

    Rather than managing the symptoms of the disease, they would be used to regenerate the affected parts of the body.

    "We're looking at the perfect human brick," said Dr Chris Mason, of the UK National Stem Cell Network.

    "Ethical, flexible and not rejected by the patient because it comes from the patient themselves."

    However, as yet, it is not a question of eliminating the use of embryonic stem cells - as some demand - but significantly expanding the existing "tool box".

    Heart cells

    In the UK, researchers in Nottingham are currently using IPS to examine heart conditions.

    By taking skin cells from diseased patients, returning them to their embryonic form before redirecting them to becoming heart cells, a greater understanding of how heart disease develops can be gained, said Dr Chris Denning, of the University of Nottingham.

    They can also be used to test drugs - potentially paving the way for more effective treatments.

    But the actual transplantation of cells remains a long way off, as scientists have not yet been able to create the volumes needed.

    There are also risks involved in any therapy. At present the stem cells need to be genetically modified in order to activate them.

    But inserting genes can be dangerous, as they can inadvertently switch on cancer-causing oncogenes.

    Scientists hope to reach a point in "the next few years" where no genetic modification is needed at all.

    But they warn that even when there may be risks, a "safety-crazed society" should not stand in the way of what may be an effective treatment for some people.

    "Obviously we want to make it as safe as possible," said Dr Mason.

    "But as long as we quantify the risks and patents understand them - are able to put them in context - the choice should be there."

    Source: BBC News © BBC 2008 (07/04/08)

    Stem-cell claim gets cold reception
    A Californian biotech company claims that it has used carbon nanotubes to ‘reprogramme’ adult human cells to an embryonic-like state — a breakthrough that removes the elevated risk of cancer that blights other techniques. But uncertainties about the cells, which have yet to be reported in a peer-reviewed journal, have left many sceptical.

    Last year, researchers led by Shinya Yamanaka of Kyoto University demonstrated that by using just four genes it was possible to reprogramme adult human skin cells to a stem-cell-like pluripotent state — meaning that they could develop into any of the body’s cell types. These ‘induced pluripotent stem’ (iPS) cells hold tremendous therapeutic potential. But to insert the genes into the cells, researchers have had to use viral vectors, which can turn the cells cancerous.

    PrimeGen, based in Irvine, claims to have got around this problem by using single-walled carbon nanotubes — cylinders of carbon molecules only a few nanometers in diameter — to introduce a complex of around a dozen proteins, including the ones coded for by the four genes used by Yamanaka, plus a fifth called Nanog. The researchers used the nanotube delivery system to introduce genes into human testicular and retinal cells, and PrimeGen reports that they were quickly taken up by an impressive 80% of the cells.

    The method is based on work by Hongjie Dai of Stanford University in Palo Alto, California. Dai’s group has demonstrated that nanotubes can deliver cancer-targeting drugs1, proteins and DNA2 into cells. According to Dai, the nanotubes with their cargo are absorbed by the cells through endocytosis, a process by which the cell membrane envelopes molecules outside the cell, but there is uncertainty over how this happens.

    PrimeGen has now announced an alliance with Unidym, based in Menlo Park, California, which makes the nanotubes. Robert Bismuth, vice president of marketing at Unidym, says that the researchers used nanotubes because they “are quite good at getting through a cell membrane” and because their long tubular structure enables each to carry several molecules.

    But on the bigger claim that they can reprogramme cells, PrimeGen president John Sundsmo admits a few problems. He says that from around day three the cells start acting like embryonic stem cells and expressing proteins characterizing pluripotency. But after day 14 “they almost all stop”. “It’s like a switch is turned on and then turned off,” Sundsmo says. True embryonic stem cells and iPS cells exhibit pluripotent markers and proliferate quickly and endlessly.

    Konrad Hochedlinger, a stem-cell researcher at Harvard University who has done some of the most rigorous tests on iPS cells, suggests that the introduced factors produced a momentary blip of activity before being diluted. “These findings are less interesting as they may only reflect transient transcriptional changes but not stable cellular changes,” he says.

    However, Sundsmo says that the cells show a stable “intermediate” stage of reprogramming that will be useful for therapy and basic research. He admits however the word “intermediate” is “loose and somewhat arbitrary”. “There is a disconnect between pluripotency and proliferation,” he says. “We haven’t figured it out yet.” Sundsmo says that they await results of a teratoma test — where cells are allowed to develop in vivo — that could prove whether the cells actually are pluripotent.

    Frank Edenhofer, a stem-cell expert at University of Bonn in Germany, calls the technique “attractive and promising”. But his own experiments have shown nanoparticles to be “toxic and display low efficiency”. Other groups have also found that nanotubes can kill cells and have difficulty releasing their cargo. Matt Becker of the National Institute of Standards and Technology in Gaithersburg, Maryland, says that the ability of nanotubes to transfect cells without doing harm “depends critically on how the materials were prepared, dispersed in solution, and specific mechanism of entry into the cell interior”.

    Few scientists have seen PrimeGen’s cells. One, Peter Donovan, a stem-cell expert at the University of California in Irvine and a member of PrimeGen’s advisory board, says: “They look really good. But what I’d really like to see is the paper published.”

    Most scientists contacted by Nature have expressed scepticism because PrimeGen announced its findings on 26 February at an investors meeting rather than in a scientific publication. Another PrimeGen scientific advisory board member, stem-cell pioneer Rudolf

    Jaenisch of the Massachusetts Institute of Technology in Cambridge, told Nature, without giving a reason, that he quit the board the following day. PrimeGen seemed unaware of Jaenisch’s move when contacted by Nature. Sundsmo says that they decided to announce the results ahead of publication because the company has already filed patent applications. He says: “This is conceptually a very simple observation that is easily repeated.”

    Two years ago, PrimeGen similarly publicized experimental results describing the derivation of pluripotent stem cells from sperm precursor cells (see Nature 440, 586–587 ; 2006). At the time PrimeGen told Nature they would publish a paper, but haven’t. Sundsmo says that the science behind that paper, which has been at the core of the company’s technology, had to be reformulated because of internal disagreement over what the experiment showed. Sundsmo says that half the company was let go and that the paper has been accepted for publication.


    1. Feazell, R. et al. J. Am Chem. Soc. 129, 8438–8439 (1997).
    2. Kam, N. W. S. et al. Angew. Chem. Int. Edn 44, 4782–4785 (2005).

    Source: Naturenews © 2008 Nature Publishing Group (10/03/08)

    Device able to pull stem cells from blood

    A tiny, implantable device can pull adult stem cells out of a living rat with greater purity than any present technique, a U.S. study found.

    The device was designed by Michael R. King, who was studying how white blood cells, called neutrophils, know how to migrate to a point of infection. He observed that near an injury, the walls of the nearby blood vessels expressed an adhesive protein and if passing neutrophils brushed against selectins they stick to the vessel wall, but did remain struck, the neutrophils rolled to the site.

    Together with Jane Liesveld, a hematology clinician doing work on bone marrow stem cells at the University of Rochester, King found that the basic rolling mechanism was the foundation of a number of other processes, including stem cell transplantation -- a natural phenomenon where stem cells move in and out of bone tissue via the blood.

    In the study, published in the British Journal of Haematology, the researchers implanted the device in a living rat and they were able to capture stem cells straight out of the bloodstream,

    "One of our ultimate goals is to develop an implantable device that will selectively remove metastatic cells from the blood," King said in a statement.

    Source: United Press International © 2008 United Press International. All Rights Reserved.

    Autologous mesenchymal bone marrow stem cells: Practical considerations in Multiple Sclerosis.
    A number of practical problems need to be addressed before any form of cell therapy can be widely applied in patients with multiple sclerosis.

    The choice of cell type is one considered elsewhere in this issue; others include the question of axon loss, that of continuing inflammatory disease activity, the mode of delivery of cells (bearing in mind the presence of innumerable lesions scattered throughout the CNS), the problem of measuring directly or indirectly the impact (if any) of an intervention, the timing of any treatment and perhaps above all the safety of the patient. All converge on the one increasingly relevant underlying question: when should stem cell treatments begin to be tested in patients?

    Here we review the progress in various of these practical problems in order to explain how we have arrived at the conclusion that the clinical science has progressed to a stage where the 'translation threshold' can be safely and appropriately crossed, and therefore why we have already commenced in Bristol a small pilot/feasibility study of autologous bone marrow cell treatment in patients with multiple sclerosis.

    Scolding N, Marks D, Rice C. University of Bristol Institute of Clinical Neurosciences, Department of Neurology, Frenchay Hospital, Bristol BS16 1LE, UK.

    Source: Pubmed - 1: J Neurol Sci. 2008 Feb 15;265(1-2):111-5. (23/01/08)

    Stem Cells From Testes Produce Wide Range of Tissue Types
    U.S. researchers say they've successfully reprogrammed adult stem cells from the testes of male mice into a wide variety of cell types, including functional blood vessels, contractile cardiac tissue, and brain cells.

    If the same can be done with adult testes stem cells from humans, they may offer a source of new therapies to treat men with health problems such as heart disease, vascular diseases, diabetes, stroke, Parkinson's, Alzheimer's, and even cancer, the researchers said.

    The study, by Howard Hughes Medical Institute scientists, is published in the Sept. 20 issue of the journal Nature.

    Only a small subset of adult testes cells have the ability to develop into multiple cell types. Until now, scientists haven't had the means to identify and isolate these stem cells.

    In this new study, the researchers reported that they had identified a novel cell surface marker called GPR125 that's expressed on a unique set of cells within adult testes -- spermatogonial stem and progenitor cells (SPCs).

    Using GPR125, the scientists were able to identify and harvest a large number of SPCs from adult mouse testes. In the lab, the team propagated and reprogrammed the SPCs to become stem cells that could differentiate into a variety of cell types.

    "It appears that these specialized GPR125-positive spermatogonial cells could be an easily obtained and manipulated source of stem cells with a similar capability to form new tissues that we see in embryonic stem cells," study author Shahin Rafii, of Weill Cornell Medical College in New York City, said in a prepared statement.

    For male patients, this "could someday mean a readily available source of stem cells that gets around ethical issues linked to embryonic stem cells. It also avoids issues linked to tissue transplant rejection, since these autologous cells come from the patient's own body," Rafii said.

    Source: Howard Hughes Medical Institute (20/09/07)

    Thailand Biotech Company Gets BOI Seal Of Approval For Adult Stem Cells
    Thailand's Board of Investment has announced its approval for TheraVitae, an Israeli-Thai company, thus paving the way for the company to expand its research and development and provide therapies using adult stem cells.

    President of TheraVitae Thailand, Mr Narin Apichairuk, said, "We are delighted to gain BOI approval because it means we can continue with our plans to open a laboratory near Bangkok and proceed with expansion of our services. To date over two hundred no-option heart patients have been treated with our patented product, VesCell, here in the kingdom. This approval means that we are seen by the Thailand government as being transparent and accountable in our operations and thus opens the way for tremendous growth and expansion."

    The company can now proceed with planning the world's largest stem cell laboratory. When completed the facility will be able to produce 1000 batches of stem cells per month. At present blood withdrawn from patients has been flown to Israel for the processing of the stem cells into therapeutic numbers.

    "The approval also facilitates in easing the requirements to bring in overseas scientists, technicians and state-of-the-art equipment. In the near future we will be able to have a knowledge transfer to local technicians. We will be able to rapidly develop further technology that will have a profound impact on the lives of many who are suffering from severe heart diseases" said Apichairuk.

    Stem cell therapy using patients' own blood has been proven beneficial in clinical trials. Around 75 percent of patients are experiencing symptom reduction and are able to take up exercise and activities that were previously denied them because of the nature of their illness. Many have been told that short of a heart transplant there is nothing more that can be done for them. Their recovery stories after adult stem cell therapy are inspiring many others to seek the help that is available to them right now.

    "It is a real privilege to be a leader of an industry that is contributing significantly to the growth of medical tourism in Thailand, which is becoming an important source of revenue for the kingdom. Furthermore, it is deeply satisfying to be at the forefront of research and development into therapies that are truly cutting-edge. The future is very exciting as more and more diseases are being added to the list of conditions that stem cells are able to help. Regenerative medicine is the future of medicine and we are proud to play a part in its progress," said Apichairuk.

    A further benefit seen to derive from BOI approval is that the company will be able to attract more investment capital now that its operations have the government's seal of approval. "Approval gives our company credibility in the marketplace," said Apichairuk. "This means investor confidence, which will fuel expansion and therefore a price reduction. Thus, more patients will be able to be treated at a lower cost. It is our wish also to take adult stem cell therapy into regional hospitals so as to serve all the people of our nation, not just foreign patients. We want to give something positive back to our community," he said.

    Theravitae's current list of partner hospitals will certainly expand as the result of BOI approval. At present Thailand partner hospitals include Bangkok Heart Hospital, Chaophya Hospital, the Phaya Thai Hospital group and Praram 9 Hospital. These prestigious hospitals bring eminent medical specialists such as Dr. Kit Arom, Professor Supachai and Dr. Eugene Sim as keen advocates of adult stem cell therapy. The company also has a relationship with Singapore's Parkway Hospital group who are using VesCell throughout their group.

    For a relatively young company at the very cutting edge of regenerative medicine, Theravitae's progress is admirable. Just last year they received the World Economic Forum "Pioneer Award" for their groundbreaking stem cell technology. This award puts them on a par with Google, another recipient of this prestigious award.

    BOI approval will spur further growth, development and innovation in bringing the latest technology to aid those suffering from a variety of devastating diseases.

    Source: Medical News Today © 2007 MediLexicon International Ltd (30/05/07)

    Research Provides New Clues about How Adult Stem Cells Work

    A new study shows that not only do stem cells from the patient’s own body readily repair all sorts of damaged tissue, they stimulate the growth and differentiation of existing stem cells. Dr. Darwin J. Prockop, Director of Tulane University’s Center for Gene Therapy says his research suggests multiple strategies to treat diseases using adult stem cells.

    Injected stem cells taken from bone marrow transfer mitochondrial DNA to existing local cells whose own mitochondria are inactive and stimulates those cells to start working.
    While scientists and doctors are seeing increasing success with treatments using adult stem cells, the actual mechanism by which the cells are able to repair and even replace damaged tissue has remained largely a mystery.

    It has been shown that even small numbers of stem cells taken from a patient’s own body, often from bone marrow, have been used successfully to treat Parkinson’s disease, kidney and liver disease, diabetes and various forms of heart disease and cancer.

    Speaking at the American Association of Anatomists in Washington April 19, Prockop described experiments in which human stem cells were injected into diabetic mice. The cells traveled to and engrafted themselves into the pancreas. They increased the production of insulin and lowered the mice’s blood sugar.

    The cells also engrafted themselves onto the kidneys and repaired the damage normally associated with diabetes.

    Source: Life Site (c) Copyright: (01/05/07)

    Stem cell researchers study reprogrammed adult cells
    A newly published study by UConn researchers confirms the potential of reprogramming cells by cell fusion.

    The technique can create stem cells for use in research, without harming embryos.

    The study is likely to intensify mounting scientific interest in reprogramming ordinary adult cells – somatic cells – back to their pristine condition when they were stem cells in the embryo.

    The researchers, led by Theodore Rasmussen of UConn’s Center for Regenerative Biology; Rachel O’Neill of the Department of Molecular and Cell Biology; and Winfried Krueger of the UConn Health Center’s Department of Genetics and Developmental Biology, reported their findings in the online edition of Stem Cells, a highly regarded journal that focuses on stem cell research. Dominic Ambrosi, a doctoral student in molecular and cell biology, is first author on the paper.

    “Our results show conclusively that factors in embryonic stem cells can reprogram the somatic genome, providing a possible avenue to create pluripotent stem cells without cloning,” says Rasmussen.

    Stem cells are the master cells that develop into the many different types of specialised cells that make up the body.

    The potential of embryonic stem cells to become virtually any kind of cell in the body is known as pluripotency.

    Currently, the only sure way to get pluripotent stem cells is to extract them from surplus frozen embryos or from embryos created through nuclear transfer – a procedure also known as therapeutic cloning.

    Either way, the process is controversial, because extraction destroys the embryo; critics regard this as tantamount to abortion.

    But recent studies have shown that pluripotency may exist in certain cells that aren’t in embryos.

    Because every cell in the body has the same genetic makeup, or DNA, the process of development starts with a cell that could become anything, but specialises to become liver, or brain, or heart, or muscle, or skin.

    To become specialised, cells acquire different patterns of gene expression, with some genes turned on while others remain silent.

    Scientists have hypothesised that if the patterns of gene expression that produce specialisation could be undone, and the process were run in reverse, cells from liver, heart, brain, muscle, or skin could be returned to stem cells like those from which they began.

    Reprogramming seeks to switch on or off the appropriate genes to transform an adult cell back to the equivalent of an embryonic stem cell.

    This method could, in theory, mass produce stem cells while bypassing entirely the problems posed by the use of frozen or cloned embryos.

    The research published by Rasmussen and his colleagues at the Center for Regenerative Biology and the Health Center is based on mouse cells.

    Following earlier experiments that demonstrated adult cells could be reprogrammed back into pluripotent stem cells, the UConn researchers blended mouse embryonic stem cells with mouse adult cells in a special chemical mixture.

    After 12 days, several hybrid cell colonies were identified and selected for further culture. From these, the team was able to establish four stable stem cell-like lines, which they used to study gene expression from the hybrid cells.

    Monitoring the hybrid cells, the UConn team discovered patterns of gene expression that made it clear the cells in the clusters were not simply the sum of the expression patterns of the parental fusion partners.

    Some genes were silenced, while others were activated, demonstrating that the adult cells had been reprogrammed.

    Rasmussen says the UConn researchers chose the mouse for their study because its genome – the entire DNA sequence of an organism – has been mapped, and that is key to understanding the structure, organisation, and function of DNA in mouse chromosomes.

    “Now we can look at which genes are being expressed and get an idea of which genes are important for reprogramming because we know the complete DNA sequence of the mouse genome in the somatic cells,” Rasmussen says.

    “We can distinguish the gene expression that arises from chromosomes of somatic cell origin from gene expression arising from chromosomes of embryonic stem cell origin.

    “In future studies, the next step will be to try and manipulate those genes,” he adds.

    If scientists can understand the process, the information may ultimately provide a basis for comparative studies with human embryonic stem cells.

    “We may be able to produce reprogrammed human cells someday soon, based on the knowledge that we have obtained with the mouse system,” Rasmussen says.

    “Such an advance could lead to the production of pluripotent human cells with therapeutic value that will not be rejected by the prospective patient’s own immune system.”

    Source: The UConn Advance© University of Connecticut 2007 (02/04/07)

    Research project tackles 'regeneration' gap
    Researchers at the McKnight Brain Institute of the University of Florida have initiated a project to treat human brain and other diseases by plundering the secrets of regeneration from creatures with remarkable powers of self-renewal, such as salamanders, newts, starfish and flatworms.

    Fueled by about $6 million in private donations, university support and state matching funds, "The Regeneration Project" will connect scientists who work with adult human stem cells — the building blocks of self-renewal that exist within our brain, bone marrow and blood — with scientists who study how tissues and limbs develop in a variety of organisms.

    "A salamander can be injured to the point that it loses its limbs or part of its spinal column, yet a few weeks later you’ll see it scurrying across your lanai," said project leader Dennis A. Steindler, Ph.D., executive director of UF’s Evelyn F. and William L. McKnight Brain Institute. "The Regeneration Project will focus on unlocking the mysteries in living, simple organisms that sustain successful tissue and organ regeneration following injury and disease, and then applying this knowledge toward encouraging repair in the more complex human, where regeneration is not so simple."

    Steindler said the project will involve researchers from far-ranging disciplines, including scientists who study how vertebrate development began millions of years ago as well as scientists who are trying to treat blindness by influencing the activity of stem cells in the human eye. In terms of brain diseases, scientists may look at ways to mobilise and reinforce the body’s own supply of adult stem cells to protect against or fight Alzheimer’s and Parkinson’s diseases, cancer, multiple sclerosis and traumatic injury.

    The project has received support from two private gifts — from Jon and Beverly Thompson of Sanibel, Fla., and from the Thomas H. Maren Foundation, based in Gainesville — and from the UF Office of Research. Initial funding will help provide fellowships for young scientists who will bridge the gaps between the different labs and investigators involved in regeneration research.

    "The fellows will be the glue that holds this broad group of scientists together," said Steindler, a professor of neuroscience at the UF College of Medicine. "We will begin a process of sharing ideas and designing experiments to answer questions about growth in simple systems that can then be applied to more complex tissue reconstruction needed in human organisms."

    Although human organ systems such as the liver are quite capable of regeneration, the brain has only a small quantity of adult stems cells to fight disease or injuries. Similarly, the body has limited capacity to repair injured limbs or spinal cords. Regeneration researchers seek to strengthen the body’s inherent healing powers.

    "We are bringing together the best of the developmental biology world with the best of the stem cell world and starting the conversation, with the focus on how to get regeneration to work in a mammal," said Edward Scott, Ph.D., a professor of molecular genetics and director of the Program in Stem Cell Biology at the College of Medicine. "Essentially, our body can heal itself, and that’s why many of us live to be 80. But we can’t do things like grow an arm or finger as we did in the early stages of our development. We want to learn how to turn those systems back on in people."

    Recently, studies have shown humans possess some of the same genes and communication pathways used by some of nature’s most remarkably regenerative animals.

    Already, UF McKnight Brain Institute scientists have discovered more than 100 genes associated with all major human neurological diseases in a simple marine snail, as well as more than 600 genes that control development. In the realm of adult human stem cells, Brain Institute researchers have shown ordinary human brain cells can generate new brain tissue in mice and produce large amounts of new brain cells in culture for use as possible replacements for dead or injured cells.

    The UF project is "bold" because it takes a comprehensive view of regenerative medicine, according to Arlene Y. Chiu, Ph.D., director for scientific activities at the California Institute for Regenerative Medicine.

    "We are all excited by the great potential of stem cells to repair damage and return function," Chiu said. "It remains a great mystery, however, why some organisms are able to renew tissues, organs and even restore whole limbs while other related animals are not. Even within a single organism, we find that some tissues have a far more robust ability to replenish and replace cells than others. Yet we do not understand the bases for these differences."

    The Regeneration Project will shortly begin establishing its think tank of international scientists, Steindler said.

    Source: University of Florida (02/04/07)

    Medistem Laboratories Announces Tolerostem(TM) Platform as Second Pipeline Product for Potential U.S. Commercialisation
    Product Aims to Reprogram Immune System, Providing New Therapy for Autoimmune Diseases and Transplant Rejection.

    Medistem Laboratories, Inc. announced today its second pipeline candidate, Tolerostem(TM), a cellular therapy platform aimed at controlling harmful immunological responses through the use of adult stem cells undergoing a proprietary modification.

    If approved for human use, the Tolerostem(TM) platform could make a significant contribution in the treatment of multiple autoimmune diseases ranging from rheumatoid arthritis, to multiple sclerosis, to Type I diabetes. Additionally, Tolerostem(TM) offers the possibility of "tricking" the immune system of transplant recipients, so as to prevent the need for chronic immune suppression, which has been shown to cause significant adverse effects.

    The Tolerostem(TM) platform is based on the fundamental concept that the regulatory T cell, a type of anti-inflammatory cell in the immune system is activated by stem cells of specific lineages. Regulatory T cells subsequently home to areas of pathological inflammation and "teach" the inflammatory cells to stop attacking the host's tissue. If successful, Tolerostem(TM) opens the door to a therapeutic approach whereby the body regulates itself without the need for other types of medical intervention.

    "Proof-of-principle that stem cells are capable of controlling harmful immune responses is being demonstrated by companies such as Osiris Therapeutics who are in Phase III clinical trials" said Neil Riordan Ph.D, President and CEO of Medistem. "Our Tolerostem(TM) platform leverages these prior successes with the aim of introducing a simple, patient-specific solution that could be widely commercialised."

    Thomas Ichim, Medistem's Chief of Scientific Development, added, "While circumstantial evidence of stem cell mediated immune modulation has been suspected for some time, we believe based on clinical data from our licensees, that we have identified a completely novel use for manipulated stem cells. This application is covered directly and indirectly in several Medistem patent applications."

    Currently Medistem is in discussions with immunology laboratories for performing preclinical safety and efficacy experiments to hopefully enable Investigational New Drug (IND) filing with the FDA in the last quarter of 2007. If accepted by the FDA, the company will then work towards initiating U.S. clinical trials.

    Source: Medistem Laboratories (21/03/07)

    MIT bioengineer advances survival, promise of adult stem cells
    MIT researchers have developed a technique to encourage the survival and growth of adult stem cells, a step that could help realise the therapeutic potential of such cells.

    Adult stem cells, found in many tissues in the body, are precursor cells for specific cell types. For example, stem cells found in the bone marrow develop into blood cells, bone cells and other connective tissues, and neural stem cells develop into brain tissue.

    Those stem cells hold great promise for treatment of injuries and some diseases, says MIT professor of biological engineering Linda Griffith.

    Griffith is the senior author of a recent study showing that when presented in the right physical context, certain growth factors encourage the survival and proliferation of bone marrow mesenchymal stem cells grown outside of the body.

    The work offers hope that one day, stem cells removed from a patient could be transplanted to an injury site and induced to grow into new, healthy tissue. The research appears in the January 18 online issue of Stem Cells.

    Griffith's team focused on the potential for mesenchymal stem cells to grow into new bone in patients with bone cancer or severe bone injuries. Current treatment for such patients involves replacing the bone with either cadaver bone or, more commonly, a piece of the patient's hip bone.

    Ideally, surgeons would like to be able to aspirate bone marrow from the hip, which is a much less painful and invasive process than removing bone, and transplant the stem cells from that marrow into the injury site.

    Although patients' own marrow has been used successfully in certain situations, Griffith and her clinical collaborators believe that the inflammatory response following transplant may limit survival of cells under many clinical conditions.

    To avoid that deadly response, Griffith and her team sought a way to manipulate the environment surrounding the cells to make conditions more favourable for survival. They zeroed in on a growth factor known as EGF, which plays a role in growth and differentiation of many cells, including stem cells. However, its ability to protect stem cells against the sort of pro-death signals found at the implant site was previously unknown.

    When EGF attaches to receptors on the stem cell surface, it activates many pathways that can influence stem cell proliferation, migration and differentiation. However, the cell normally absorbs EGF and degrades it, and the growth factor loses its power to influence cell behaviour. This has made EGF notoriously difficult to develop as a clinical product for wound healing.

    To control this, the researchers decided to tether EGF to a scaffold, preventing the stem cells from eating it up and allowing continuous EGF exposure on the cell surface.

    "Putting them on a scaffold is appealing because then you can control the concentration and location and so forth," Griffith said. The ceramic and polymer scaffold, which remains in the patient's body during healing but then resorbs, also provides structure for the stem cells as they grow into new bone cells.

    "We found that when EGF was tethered to the surface it elicited different cell responses than it did when given to cells in the usual soluble form," Griffith said. "When tethered, it protected the cells from being killed by pro-death inflammatory signals. The soluble version of the factor did not protect cells."

    So far all of the experiments have been done in vitro, or outside the body, but the researchers are currently planning studies in animals.

    Griffith, who does not work with human embryonic stem cells, believes that adult stem cells offer promising therapeutic possibilities.

    "I'm very optimistic about the potential for adult stem cells to be useful clinically for the problems I work on, since there are already some clinical successes based on these cells" she said. "Continuing, careful, methodical work will lead to improved therapies based on adult stem cells. We are aiming to expand the range of therapies that work in the clinic." Griffith is one of several MIT biological engineering faculty members who work with adult stem cells but not human embryonic stem cells.

    Griffith is also one among many scientists around the world who have at least some objections to creation of human embryonic stem cells, for a variety of reasons. She says her current focus on adult stem cells is driven largely by the interesting science and the feasibility for near-term clinical use for the types of cells she investigates. However, she also avoids research with human embryonic stem cells following a personal experience with in vitro fertilization almost 10 years ago.

    "Like some other scientists I know, my personal views about creating human ES cell lines changed when confronted with the reality of doing so from my own embryos. After this experience, I was not comfortable conducting human ES cell research myself, and I have a better understanding of why some scientists object to all work with human ES cells," she said. She also said she feels her personal views, and those of others, are respected in the scientific community.

    Currently, federally funded research is only allowed on certain established lines of embryonic stem cells, although a few states, including California and Connecticut, offer state funding for broader embryonic stem cell research. There are no legal restrictions on funding to study adult stem cells.

    Griffith's recent work was funded by the National Institutes of Health and the Harvard School of Dental Medicine.

    The lead author on the Stem Cells paper is Vivian Fan, a graduate student in MIT's Department of Biological Engineering and the Harvard School of Dental Medicine. Other authors are Ada Au and John Wright, graduate students in the Department of Biological Engineering; Romie Littrell, lab manager in Griffith's lab; Llewellyn Richardson, research assistant in the Department of Chemical Engineering; and Kenichi Tamama and Alan Wells of the University of Pittsburgh.

    Source: Massachusetts Institute of Technology (27/02/07)

    Study showing promise of adult stem cells was flawed, scientific panel finds
    A scientific panel says a 2002 study that suggested adult stem cells might be as useful as embryonic ones was flawed and its conclusions may be wrong, a finding that raises questions about the promise of a less controversial source for stem cells.

    The research by Catherine Verfaillie at the University of Minnesota concluded that adult stem cells taken from the bone marrow of mice could grow into an array of biological tissues, including brain, heart, lung and liver.

    So far only embryonic stem cells, which are commonly retrieved by destroying embryos at an early stage of development, are known to hold such regenerative promise. Many scientists believe they might one day be used to treat certain diseases and other conditions.

    Opponents of stem cell research seized on the 2002 findings as evidence that stem cell science could move forward without destroying embryos. But Verfaillie has acknowledged flaws in parts of the study after inquiries from the British magazine New Scientist, which first publicised the questions last week.

    A panel of experts commissioned by the university concluded that the process used to identify tissue derived from the adult stem cells was ``significantly flawed, and that the interpretations based on these data, expressed in the manuscript, are potentially incorrect,'' according to a portion of the panel's findings released by the university.

    The panel concluded that it wasn't clear whether the flaws mean Verfaillie's conclusions were wrong. It also determined that the flaws were mistakes, not falsifications.

    Tim Mulcahy, vice president of research at the university, said it would be up to the scientific community to decide whether Verfaillie's study still stands up.

    ``From her perspective, the findings stand. I think the scientific community will have to make their own opinion,'' he said.

    Other researchers have been unable to duplicate Verfaillie's results since the 2002 publications, increasing their skepticism about her claims. But that may only be an indication of how difficult the cells are to work with, said Amy Wagers, a Harvard University stem cell researcher who was not involved in the investigation.

    Verfaillie did not respond to a phone message left with her current employer, the Catholic University of Leuven in Belgium. She told the Star Tribune of Minneapolis in a story published Friday that the problem was ``an honest mistake'' that did not affect the study's conclusions about the potential of adult stem cells.

    Her research was scrutinized after a writer for New Scientist noticed that some data from the original 2002 article in the journal Nature duplicated data in a second paper by Verfaillie around the same time in a different journal, even though they supposedly referred to different cells. Verfaillie told the Star Tribune that the duplication was an oversight and said she notified the University of Minnesota, which convened the panel to take a closer look at the research.

    The editor of the London-based scientific journal Nature said in a statement, ``We are in touch with the author and investigating the problems that have been mentioned. We have no further comment.''

    Dr. Diane Krause of Yale University, who (like Verfaillie) has studied using bone marrow as an alternative to embryonic stem cells, said she believes Verfaillie's research will hold up, despite being hard to repeat.

    ``When it comes to Catherine, she's impeccable. She's one of the most careful scientists I know,'' Krause said.

    Nigel Cameron, who runs the Institute on Biotechnology and the Human Future and is a bioethics professor at Chicago-Kent College of Law in the Illinois Institute of Technology, said scientists who have been trying to find a middle way on stem cells have seen their work seized by one side or the other for their own advantages.

    ``This is a fascinating example of the way in which science is becoming politicised, on both sides of this debate,'' said Cameron, who supported President Bush's 2001 ban on federal dollars spent on deriving new stem cells from fertilized embryos. ``It's no longer scientists in white coats coming up with facts. There are uses being made of the facts on all sides, and I think it's quite problematic.''

    Source: © Copyright 2007 The Kansas City Star. All Rights Reserved (24/02/07)

    Stem Cells Cultured From Human Bone Marrow Behave Like Those Derived From Brain Tissue
    Stem cells taken from adult human bone marrow have been manipulated by scientists at the Maxine Dunitz Neurosurgical Institute at Cedars-Sinai Medical Center to generate aggregates of cells called spheres that are similar to those derived from neural stem cells of the brain.

    In addition, the bone marrow-derived stem cells, which could be differentiated into neurons and other cells making up the central nervous system, spread far and wide and behaved like neural stem cells when transplanted into the brain tissue of chicken embryos.

    Results of the experiments, described in the February 2007 of the Journal of Neuroscience Research, support the concept of using bone marrow-derived stem cells to create therapies to treat brain tumors, strokes and neurodegenerative diseases. A similar study using bone marrow-derived stem cells of rats appeared as the cover article of the December 2002 issue of Experimental Neurology.

    "These findings reinforce the data that came from our study of rat bone marrow-derived stem cells," said John S. Yu, M.D., neurosurgeon, co-director of the Comprehensive Brain Tumor Program, and senior author of both articles. "Using two methods, we show evidence for the bone marrow-derived stem cells being neural cells, and we demonstrate that it is feasible to grow the cells in large numbers. We also document that these cells function electrophysiologically as neurons, using similar voltage-regulating mechanisms."

    Progressing from the rat study to experiments with human cells and transplantation into mammal brain tissue, the research team continues to build a foundation for translating laboratory research into human clinical trials.

    "Based on our studies to date, a patient's own bone marrow appears to offer a viable and renewable source of neural stem cells, allowing us to avoid many of the issues related to other types of stem cells," said Keith L. Black, M.D., director of the Maxine Dunitz Neurosurgical Institute and chairman of Cedars-Sinai's Department of Neurosurgery.

    The replacement of damaged brain cells with healthy cells cultured from stem cells is considered to potentially be a promising therapy for the treatment of stroke, neurodegenerative disorders and even brain tumors, but finding a reliable source for generating neural cells for transplantation has been a challenge. The use of embryonic and fetal tissue has raised ethical questions among some, and brings with it the possibility of immune rejection. And while neural stem cells can be taken from brain tissue, the removal of healthy tissue from a patient's brain introduces a new set of safety, practicality and ethical issues.

    In their recent work, the Cedars-Sinai researchers documented that several genes that speed up and control the proliferation process could be used to rapidly expand the supply of marrow-derived neural stem cells, writing in the article that "this novel method of expansion ... may prove to be useful in the design of novel therapeutics for the treatment of brain disorders, including tumors."

    The study was supported by grants from the National Institutes of Health.

    Citation: Journal of Neuroscience Research, Feb. 2007, "Manipulation of proliferation and differentiation of human bone marrow derived neural stem cells in vitro and in vivo"

    Source: Cedars-Sinai Medical Center (25/01/07)

    New nerve cells in diseased brain
    Nerve cells generated from stem cells in an adult, diseased, and damaged brain function as normal nerve cells. This has been shown at Lund University in Sweden in a new study published in the prestigious journal Neuron. The new nerve cells also seem to have a positive function, namely, to counteract the disease in the brain.

    Until the middle of the 1990s researchers believed that new nerve cells could not be generated in the adult brain. Then it was found to be possible, and that new nerve cells are formed not only in healthy brains but also in brains affected by disease and damage. Professor Olle Lindvall, Assistant Professor Zaal Kokaia, and their associates at Lund University were the first scientists to demonstrate that new nerve cells could be created from the stem cells of an adult brain following a stroke and then migrate to the damaged area.

    However, it has been unclear just how these new nerve cells function. Do they behave normally, and are they beneficial or detrimental to a diseased brain? For the first time, Professor Olle Lindvall, Assistant Professor Merab Kokaia, doctoral candidate Katie Jakubs, and others have now managed to answer these questions on the basis of experiments on rats.

    "Our study shows that nerve cells that are generated from stem cells in an adult epileptic brain develop into normal nerve cells. Interestingly, they also join up with other nerve cells in a way that indicates they are trying to counteract the diseased function," says Olle Lindvall.

    This work, carried out at the Section for Restorative Neurology and the Stem Cell Center at Lund University, is basic research, but it has potential clinical applications down the road. By learning more about how new nerve cells are formed and how they function, it may be possible in the future to help the brain heal itself after a disease or injury.


     Source: idw © 1995-2006 Informationsdienst Wissenschaft e.V. - Impressum (21/12/06)

    Stem cells found in adult hair follicles may provide alternative to embryonic stem cells
    Having recently identified the molecular signature of these epidermal neural crest stem cells in the mouse, their research resolves conflicting scientific opinions by showing that these cells are distinctly different from other types of skin-resident stem cells/progenitors. Their work provides a valuable resource for future mouse neural crest stem cell research.

    A report on the research from Dr. Maya Sieber-Blum's laboratory, co-authored by Yao Fei Hu, Ph.D., and Zhi-Jian Zhang, Ph.D., researchers in cell biology, neurobiology and anatomy at the Medical College, was published in a recent issue of Stem Cells: The International Journal of Cell Differentiation and Proliferation.

    Epidermal neural crest stem cells are found in the bulge of hair follicles and have characteristics that combine some advantages of embryonic and adult stem cells, according to lead researcher, Maya Sieber-Blum, Ph.D., professor of cell biology, neurobiology & anatomy. Similar to embryonic stem cells, they have a high degree of plasticity, can be isolated at high levels of purity, and can be expanded in culture. Similar to other types of adult stem cells, they are readily accessible through a minimally invasive procedure and could lead to using a patient's own hair as a source for therapy without the controversy or medical issues of embryonic stem cells.

    "We see the potential for cell replacement therapy in which patients can be their own donors, which would avoid ethical issues and reduce the possibility of tissue incompatibility," says Dr. Sieber-Blum.

    The Medical College team in collaboration with Prof. Martin Schwab, director of the Brain Research Institute of the University of Zürich, recently injected these cells in mice with spinal cord injuries. According to the study, when grafted into the spine, the cells not only survived, but also demonstrated several desirable characteristics that could lead to local nerve replacement and re-myelination (restoration of nerve pathways and sheaths).

    Neural crest stem cells generate a wide array of cell types and tissues and actually give rise to the autonomic and enteric nervous systems along with endocrine cells, bone and smooth muscle cells. The cells can be isolated from the hair follicle bulge as multipotent stem cells, and then expanded in culture into millions of cells without losing stem cell markers.

    "We grafted the cells into mice that have spinal cord injuries and were encouraged by the results. The cells survived and integrated into the spinal cord, remaining at the site of transplantation and not forming tumors," Dr. Sieber-Blum says.

    According to Dr. Sieber-Blum, subsets of the epidermal neural crest stem cells express markers for oligodendrocytes, the nerve-supporting cells that are essential for proper neuron function. She has been awarded a grant from the Biomedical Technology Alliance, a Milwaukee inter-institutional research group, to determine in collaboration with Brian Schmit, Ph.D., associate professor of biomedical engineering at Marquette University, if the grafts lead to an improvement of spinal reflexes in the injured spinal cord of mice.

    Dr. Sieber-Blum points out that the cells may also be useful to treat Parkinson's disease, multiple sclerosis, Hirschsprung's disease, stroke, peripheral neuropathies and ALS. Certain defects of the heart, and bone defects (degeneration, craniofacial birth defects) could also be treated through neural crest stem cell replacement therapy. Together, these conditions affect over 11 million people today in the US and are estimated to annually cost more than $170 billion.

    Source: Medical College of Wisconsin (12/12/06)

    Researchers spur growth of adult brain stem cells
    Researchers have found a way to spur the growth of neural stem cells in the brains of adult mice with an eye toward harnessing the brain's innate capacity for repair to help people with diseases such as Alzheimer's.

    Determining how these stem cells can be deployed to replace cells in mice whose brains are damaged in ways resembling Parkinson's disease, Alzheimer's disease and multiple sclerosis in people is the next key step, researchers said.

    The study, appearing on Tuesday in the Journal of Neuroscience, provides a fresh example of the potential for using so-called adult stem cells to treat illness by replacing cells damaged by disease or injury.

    But Paul Patterson of the California Institute of Technology, senior author of the study, said it is important for scientists to continue to study embryonic stem cells as well.

    Patterson and colleague Sylvian Bauer injected a natural protein from the body -- leukemia inhibitory factor, or LIF -- into a part of the brain of adult mice where stem cells reside. This fostered the production of up to six times the usual count of adult neural stem cells.

    Using a person's own cells, rather than foreign cells, in future regenerative therapies avoids the transplantation of stem cells that the body's immune system might reject.

    While this study involved mice, the researchers noted that human adults also harbor neural stem cells in their brains. The brains of neurodegenerative disease patients appear to try to marshal their own neural stem cells to replace dying cells, but not in the numbers sufficient to do the job.


    "The adult brain does try to repair itself by stimulating its own neural stem cells. But obviously it's not enough. So what we're trying to do here is kick it in the pants and increase the number of neural stem cells," Patterson said in an interview.

    Stem cells are a kind of master cell for the body, producing various tissue and cell types. If researchers can figure out how to control them and direct them into changing into specific types as needed, stem cells might be able to replace tissue harmed by illness or injury.

    Those taken from days-old embryos are especially malleable, and can produce any cell or tissue found in the body, but so-called adult stem cells also have shown promise.

    Some people oppose as unethical the use of cells from human embryos in research, arguing that good research can be done using adult stem cells. Scientists are trying to develop potential treatments using both kinds of cells.

    Patterson said possible human therapies related to his research remain years away. He emphasised the importance of scientists pursuing work on adult and embryonic stem cells as they try to realise the potential of regenerative therapies.

    "My own feeling is that lots of different approaches should be tried simultaneously because we don't know which ones are going to be the most successful. So we have to push on all fronts," Patterson said.

    Source: Yahoo! News Copyright © 2006 Reuters Limited. All rights reserved. (15/11/06)

    Cord Blood to collect stem cells from fat
    Cord Blood America said Thursday it would start a service to collect adult stem cells from fat for future medical use.

    "We anticipate beginning this service in the fourth quarter of 2006," said Matthew Schissler, Cord Blood America's chairman and CEO. No further details were provided about the planned service.

    Cord Blood says that scientific studies indicate the stem cells harvested from human fat tissue have the ability to become nerve cells that could be used to treat brain and spinal-cord injuries and other disorders.

    "Research shows that this virtually limitless supply of stem cells could become any type of cell and could be used to treat diseases ranging from diabetes to Parkinson's disease," Schissler said.

    "We are confident that stem cells from adipose (fat) tissues will be a practical and appealing source of stem cells for the medical therapies of the future," he added. "There is absolutely no controversy about the use of these stem cells, and we are proud to be on the cutting edge of this field. While Congress debates these issues, we are actually taking action."

    Source: United Press International © Copyright 2006 United Press International, Inc. All Rights Reserved (21/07/06)

    New Source of Multipotent Adult Stem Cells Discovered in Human Hair Follicles
    Implications for Personalized Approaches to Transplants.

    Researchers at the University of Pennsylvania School of Medicine have isolated a new source of adult stem cells that appear to have the potential to differentiate into several cell types. If their approach to growing these cells can be scaled up and proves to be safe and effective in animal and human studies, it could one day provide the tissue needed by an individual for treating a host of disorders, including peripheral nerve disease, Parkinson’s disease, Multiple Sclerosis and spinal cord injury.

    “We are very excited about this new source of adult stem cells that has the potential for a variety of applications,” says senior author Xiaowei (George) Xu, MD, PhD, Assistant Professor of Pathology. “A number of reports have pointed to the fact that adult stem cells may be more flexible in what they become than previously thought, so we decided to look in the hair follicle bulge, a niche for these cells.” Xu and colleagues report their findings in the latest issue of the American Journal of Pathology.

    Hair follicles are well known to be a source for adult stem cells. Using human embryonic stem cell culture conditions, the researchers isolated and grew a new type of multipotent adult stem cell from scalp tissue obtained from the National Institute of Health’s Cooperative Human Tissue Network.

    The mutipotent stem cells grow as masses the investigators call hair spheres. After growing the “raw” cells from the hair spheres in different types of growth factors, the investigators were able to differentiate the stem cells into multiple lineages, including nerve cells, smooth muscle cells, and melanocytes (skin pigment cells).

    The differentiated cells acquired lineage-specific markers and demonstrated appropriate functions in tissue culture, according to each cell type. For example, after 14 days, 20% to 40% of the cells in the melanocyte media took on a weblike shape typical of melanocytes. The new cells also expressed biomarkers typical of pigment cells and when placed in an artificial human skin construct, produced melanin and responded to chemical cues from normal epidermis skin cells.

    After 14 days, about 10% of the stem cells in the neuronal cell line -- a type of cell not present in skin or hair -- grew dendrites, the long extensions typical of nerve cells and expressed neuronal proteins. The neurotransmitter glutamate was also present in the cells, but the neurotransmitter dopamine was not detected.

    Thirdly, about 80% of the stem cells grown in the muscle media differentiated into smooth muscle cells. These new muscle cells also contracted when placed in a collagen matrix.

    Overall, the researchers showed that human embryonic stem cell media could be used to isolate and expand a novel population of multipotent adult stem cells from human hair follicles. “Although we are just at the start of this research, our findings suggest that human hair follicles may provide an accessible, individualised source of stem cells,” says Xu. The researchers are now working on inducing other cell types from the hair sphere cells and testing the cells in animal models.

    Study co-authors are Hong Yu, Suresh M. Kumar, and Geza Acs, all from Penn; and Dong Fang, Ling Li, Thiennga K. Nguyen, and Meenhard Herlyn, all from the Wistar Institute, Philadelphia.

    Source: WebWire® 1995-2006 (13/07/06)

    BrainStorm Advances Its International Patent Application (PCT) for Stem Cell Procedure with Potential for Treating Parkinson's and Other Neurodegenerative Diseases
    BrainStorm Cell Therapeutics announced today that it has advanced its patent application from a provisional to an international patent application for a new procedure to derive "neuronal-supporting cells" from adult bone marrow with the US Patent and Trademark Office. The patent protects a procedure for inducing bone marrow stem cells to differentiate into astrocytes, which are brain cells that naturally support neurons in the brain. The induced cells display astrocyte-like morphology, express typical astrocyte proteins and most importantly, have the capacity to synthesize and secret neurotrophic factors, including glial-derived neurotrophic factor (GDNF). GDNF is the most potent neurotrophic factor known for dopaminergic neurons, the cells that degenerate in patients with Parkinson's disease.

    Transplanting these neuronal-supporting astrocyte cells--acting on their own or in combination with dopamine-producing cells--holds great promise for the replacement of and/or preservation of neurons in Parkinson's and other neurodegenerative diseases.

    The invention involves inducing adult bone marrow stem cells to differentiate into neuronal supporting cells using the proprietary stem cell technology developed at Tel Aviv University. The latest patent application was filed by the technology transfer company of Tel Aviv University, Ramot, on the basis of research funded by Brainstorm. Worldwide rights to the development and commercialisation of the new technology are exclusively licensed to BrainStorm.

    "Developing the capability to induce adult stem cells to differentiate into cells that secrete a battery of neurotrophic factors is a major step forward because of the important role that these factors are believed to have in brain cell survival and growth," said Yoram Drucker, Principal Executive Officer of BrainStorm. "Neurotrophic factors have the capacity to protect neurons and induce neural sprouting, and hold great promise for the treatment of many neurodegenerative diseases, including Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Spinal Cord Injury (SCI) and even Alzheimer's disease," he added.

    BrainStorm has previously announced observing a significant beneficial effect of transplanting GDNF-producing cells--derived from human bone marrow stem cells utilising the propriety technology--into animal models of Parkinson's disease. The scientific team transplanted the GDNF-producing cells into rats with Parkinson's disease, generated by specifically damaging their dopaminergic cells. Within just two weeks of cell transplantation, the team observed significant improvement in the rats' characteristic disease behaviour, including more than 50% reduction in rotational movements and enhancement in their paw reaching capacity. The beneficial effect was maintained for over four months.

    Other routes of delivery of GDNF to the disease site have proven difficult to achieve. GDNF is a protein and, as such, has limited stability and ability to penetrate the brain. Attempts made to deliver the protein directly into the brain have met with limited success. An alternative approach, to deliver GDNF by genetic therapy, suffers the limitations and risks of using viral vectors. Other cell therapeutic approaches using either genetically engineered or differentiated embryonic and neural stem cells are limited by issues of graft rejection and potential tumorogenic risk.

    "BrainStorm's approach of using patient-derived differentiated stem cells holds the promise to overcome the above pitfalls. Recognised as the patient's own cells, there should be no graft rejection. Moreover, unlike embryonic cells, the bone marrow derived-cells are not known to be tumorogenic. Thus, the newly transplanted cells are expected to survive and integrate, releasing the therapeutic GDNF in a physiological manner," said Dr. Daniel Offen, Chief Scientist.

    Source: BrainStorm Cell Therapeutics Inc. (11/07/06)

    Adult stem cells therapy - The power waiting to be unleashed
    By Sylvia Miriyam Findlay, Research Analyst, Pharmaceutical and Biotechnology

    Adult stem cells are undifferentiated cells found amidst the adult tissues. These cells are present in the tissues to aid in the repair of damaged tissues. Isolating these adult stem cells or somatic cells opens up a whole world of applications in improving healthcare.

    The adult stem cells are pluripotent (ability to differentiate into multiple cell types except the placenta). Researchers are experimenting on isolating these pluripotent adult stem cells, culturing them to grow into the desired type of cells and thereby utilising those to cure various diseases that currently lack adequate treatment options. The various therapeutic areas in which these adult stem cells can be utilised are orthopaedics, neurology, metabolic disorders, cardiology and spinal cord injuries among the others. These adult stem cells are known to exist in 13 of the 220 tissues and they have the potential to develop into any cell. Scientists are vying to utilise the potential of the adult stem cells.

    The challenges

    Identification and isolation of adult stem cells hinders progress.
    Adult stem cell therapy, which is still in the infant stage, has numerous hurdles to overcome. The primary hindrance that is plaguing the researchers is the difficulty in isolating the cells. As they reside among the differentiated tissues, it is cumbersome to be isolated and cultured. Technological advances have led to the introduction of sophisticated equipments to isolate these cells but the challenge is yet to be overcome completely.

    Scarcity and lack of versatility of Adult Stem Cells increases complexity
    Furthermore, the slow rate of proliferation of the adult stem cells poses a formidable challenge to the scientific community. The adult stem cells tend to multiply very slowly giving rise to differentiated cells. The mature, differentiated cells arising from the adult stem cells grow faster and outnumber the stem cells thereby making the stem cells isolation a complex process. The adult stem cells are therefore very rare and also lack the versatility seen in the embryonic stem cells. Adult stem cells generally tend to develop into the tissue from where they are isolated. However, experiments have shown that the adult stem cells have exhibited plasticity or transdifferentiation. Haematopoietic stem cells have been observed to develop into neural cells, cardiac cells, liver cells and skeletal muscle cells. Bone marrow stem cells have developed into cardiac and skeletal muscle cells, while the neural cells have shown to differentiate into blood cells and skeletal cells. The embryonic stem cells are totipotent (potential to develop into any cell including the placenta)

    Adult stem cell therapy-The advantages
    The inadequacy in the treatment options available and the increasing unmet needs in the healthcare arena are forcing researchers to search for greener pastures. Stem cell therapy offers to close the gap that current medications fail to close. Embryonic stem cell therapy is promising but ethical issues have retarded the progress. Scientists had to turn towards adult stem cell therapy and tap the hidden potential.

    The forthcoming benefit of using adult stem cell therapy is that the patients’ stem cells can be harvested, cultured into the desired cells and reintroduced. This procedure minimises the risk of immune rejection.

    The future
    Several unanswered questions remain with regard to adult stem cell therapy. The range of adult stem cells present in the body remains to be assessed. The plasticity or transdifferentiation of the cells has to be mapped in order to assess its significant impact on the treatment procedures. Powerful techniques to isolate the stem cells have to be developed. In addition, scientists have to unearth ways to stimulate the adult stem cells to proliferate at a rapid rate. More innovative research is required to mine the hidden potential of the adult stem cells.

    A two pronged approach is necessary to fully exploit the advantages of stem cell therapy. Adult stem cell and embryonic stem cell therapy can open wide possibilities of meeting the unmet medical needs. The importance of adult stem cell research coupled with embryonic stem cell research has to be highlighted to the healthcare community. The sensitivity surrounding the research on embryonic stem cells is hindering further development. Various organisations are currently concentrating on adult stem cell therapy and funding for the research is high in the United States.

    Adult stem cell therapy has the potential to revolutionise the field of medicine. However a yawning gap persists between the promise and fulfilment. The complexity of the genetic and biological processes involved in stem cell differentiation is yet to be deciphered. Better understanding of the signals and pathways involved in stem cell differentiation can bolster the efforts of the researchers to alleviate the pains of the suffering individuals.

    The opinions expressed in the articles published in this section do not necessarily reflect those of Pharmalicensing or Bridgehead International. No actions including proposals to or agreements with other companies should be taken by any reader without obtaining specific business or legal advice. Neither the publisher nor the authors accept any liability for any actions or activities undertaken by any reader or other third party as a consequence of these articles or for any errors or omissions therein.

    Copyright © 1995-2006 Pharmalicensing Ltd., all rights reserved. (03/07/06)

    Stem cells used to cure urinary incontinence
    Doctors say they were able to cure urinary incontinence in the vast majority of patients who were treated with injections of their own stem cells.

    The finding, which was presented Sunday, is the latest accomplishment in a promising area of research: using adult stem cells derived from patients' own muscle tissue to treat a troubling condition that affects more than 15 million Americans.

    The researchers described the treatment as a cure, meaning the patients did not need to wear pads after they were treated.

    "It's highly effective and it's much more effective than we previously thought," said lead author Hannes Strasser. "If somebody had told me it would have worked so well four years ago, I would not have believed it."

    Some of the first patients to undergo the technique remained continent four years after the treatment, said Strasser, an associate professor of urology at the Medical University of Innsbruck, in Austria.

    The results presented Sunday involved 186 men and women aged 36 to 85. The study involved about twice as many women as men.

    One year after the treatment, 153 of all of those treated did not need to wear pads, Strasser said.

    In addition to curing the incontinence, the patients also had a dramatically improved quality of life, he said.

    There were no side effects, although a later patient, one of 270 who now have undergone the therapy, suffered a perforation of the urethra during the treatment.

    The research was presented at the American Urological Association annual meeting in Atlanta.

    "It's a great idea," said Elliott Silbar, a urologist with Aurora St. Luke's Medical Center who attended the presentation. "They are trying to replace healthy cells into an area with unhealthy tissue. Theoretically, it makes a lot of sense."

    What's still needed, Silbar said, are studies involving head-to-head comparisons between the adult stem cell treatment and other types of injectable urinary incontinence treatments.

    One potential advantage to the stem cell treatment is the possibility that it only may need to be done once, compared with the need for re-treatment with other injectable therapies, he said.

    Strasser said the stem cell treatment costs about $16,000.

    The treatment involves harvesting muscle cells taken as biopsy from the patient's upper arm. Those cells are grown in a laboratory for seven weeks and a small amount of collagen is mixed in.

    "What's nice is they are using the patient's own cells," said Silbar who was not a part of the study. "You are not going to have any problem with rejection or diseases. "It's totally biocompatible."

    What is not known is whether the new cells become functioning muscle, as is theorized, or whether the injections are just providing bulk, as is the case with other treatments, Silbar said.

    The extracted cells become both myoblasts, or muscle cells, and fibroblasts, a type of connective tissue cell.

    The fibroblasts were injected into the urethra, the canal that carries urine out of the bladder. The myoblasts were injected into the rhabdosphincter, a ring of muscle around the urethra that acts as a valve.

    The treatment did not involve the use of embryonic stem cells, which generally are derived from five-day-old embryos.

    The research has created a buzz at the meeting, said Michael Guralnick, an assistant professor of urology at the Medical College of Wisconsin.

    "It almost sounds too good to be true," said Guralnick who also attended the presentation.

    One advantage to the treatment is that patient's own muscle cells can become a potential permanent rebuilding source of the sphincter muscle, Guralnick said.

    He said the cure rate cited by researchers of more than 80 percent is about twice that for other injectable treatments.

    Guralnick said the treatment still needs to be subjected to more rigorous scientific testing. And, he said, it's likely to be a few years before it is available in the United States.

    "This could really be a better alternative, but it's still in its infancy," he said.

    The injections were done using a technique known as transurethral ultrasound.

    "We can inject both types of cells very precisely," Strasser said.

    Imaging showed that the thickness of the urethra and rhabdosphincter were increased and the contracting ability of the rhabdosphincter was improved, he said.

    "It's much stronger," Strasser said.

    Other research presented Sunday indicated that the prevalence of urinary incontinence may be 50 percent greater than previously thought, affecting up to 17 percent of men over the age of 60 and 38 percent of women.

    "People are walking around (with incontinence) and not even asking their doctors about it," said Jennifer Anger, a urologist with the UCLA Medical Center in Los Angeles. "Prevalence is high in men and very high in women."

    Urinary incontinence can be caused by a variety of conditions, including childbirth, prostate surgery, diabetes, stroke, multiple sclerosis and Parkinson's disease. Many of those in the study had the most common type of urine leakage, known as stress incontinence. It occurs when urine is lost as the result of pressure on the lower abdomen from activities such as sneezing, coughing and exercise.

    Source: (22/05/06)

    Study: Bone Marrow Stem Cells May be Successful in Treating Parkinson's and MS
    The results of a study published in the April issue of Stem Cells and Development suggest that human stem cells derived from bone marrow are predisposed to develop into a variety of nerve cell types, supporting the promise of developing stem cell-based therapies to treat neurodegenerative disorders such as Parkinson's disease and multiple sclerosis.

    Stem Cells and Development, a peer-reviewed journal published by Mary Ann Liebert, Inc., carries the paper, entitled "Human Mesenchymal Stem Cells Express Neural Genes, Suggesting a Neural Predisposition." (online here

    The surprising results lend a new perspective to stem cell differentiation and suggest that multipotential stem cells may express a wide variety of genes at low levels and that stem cells achieve their remarkable plasticity by downregulating the expression of many of these background genes.

    While many scientists believed stem cells were the most primitive cells, the study suggests otherwise. In an accompanying editorial, journal Editor-in-Chief, Denis English, Ph.D., Professor of Neurosurgery and Director of Cell Biology at the Center of Excellence for Aging and Brain Repair Research at the University of South Florida College of Medicine in Tampa, writes, "contrary to our current thinking, stem cells are in no sense primitive cells. In fact, stem cells may well be the most advanced cells the organism produces."

    The authors of the report, Netta Blondheim, Yossef Levy, Tali Ben-Zur, Alex Burshtein, Tirza Cherlow, et al., from the Felsenstein Medical Research Center and Department of Neurology at Rabin Medical Center, the Sackler School of Medicine of Tel Aviv University, and Laniado Hospital in Israel, propose this new view of adult stem cell plasticity based on their findings that bone marrow-derived mesenchymal stem cells grown in the laboratory express an extensive assortment of neural genes, genes linked to the neuro-dopaminergic system, and transcription factors that control genes having neural significance.

    They conclude that these MSCs are predisposed to differentiate into neuronal cells given the proper conditions. When transplanted into the central nervous system, they will develop into a variety of functional neural cell types, making them a potent resource for cell-based therapy.

    Source: (c) Copyright: (03/05/06)

    New method invented for isolating, purifying embryonic-like adult stem cells in the blood

    Moraga Biotechnology Corporation, an adult stem cell company based in Los Angeles, California, discovered proprietary Blastomere-Like Stem Cells (BLSCs) circulating in the peripheral blood of mammals. The company's scientists found that these adult stem cells were able to differentiate into most tissues and organs of the body.

    The company's scientists have developed a proprietary and cost-effective method for isolating and purifying large numbers of its primitive embryonic-like stem cells from the blood without ex vivo expansion. Moraga recently announced that its BLSCs were found in large numbers throughout the body. The company believes this new discovery is a major breakthrough for finding large numbers of primitive adult stem cells circulating in the blood.

    Moraga's chief executive, Dr. John F. Wong, noted that the ability to isolate these primitive embryonic-like stem cells in peripheral blood allows the company to enter the stem cell banking business in the near future. With this new method for isolating stem cells, the company will be able to bank an individual's stem cells by simply withdrawing a sample of their blood.

    The company intends in the very near future to establish processing centres to which a donor's blood sample is shipped; the blood is processed; and, the stem cells are isolated. The BLSCs are then stored at the centre for future therapeutic and diagnostic use. Dr. Wong further stated, "By circumventing the expensive process of isolating and expanding the stem cells outside the body, the Company can now travel down a shorter path towards developing a near-term solution for autologous stem cell-based therapies, from which its BLSCs may be used for treating various forms of diseases such as heart attacks, Parkinson's disease and Multiple Sclerosis."

    Source: Copyright © Saffron Media Pvt. Ltd.(18/04/06)

    Adult Stem Cells Can Produce Brain Cells
    Experiments involving chicken eggs may have hatched a major advance in stem cell research, as investigators watched adult human stem cells develop into functioning brain cells.

    Experts hope that, someday, adult stem cells from a patient's own bone marrow might be used to regrow and replace brain or spinal cord cells lost to injury or disease. That goal had been elusive, however, because adult stem cells have failed to produce significant amounts of neurons.

    Until now, that is.

    "We found that bone marrow stem cells did make neurons in the environment of the regenerating embryonic [chick] spinal cord," said senior researcher Joel C. Glover, of the Institute of Basic Medical Science at the University of Oslo, in Norway.

    "This happened at a much higher rate than had been observed in any other experimental system," he added.

    The key to the success of this model lies in as-yet-unidentified compounds within the quickly developing "microenvironment" of the embryonic spinal cord, said Paul Sanberg, a professor of neurosurgery and director of the University of South Florida's Center for Aging and Brain Repair.

    Sanberg, an expert in this kind of research, believes that if scientists can identify those compounds, they might then be able to use them as a kind of cellular fertilizer -- encouraging adult stem cells to generate into human neurons.

    "This study really shows that the microenvironment a stem cell is placed in is really very critical for defining how that stem cell will work," he said.

    The findings appear in this week's issue of the Proceedings of the National Academy of Sciences.

    According to Glover, his team knew that "the spinal cord of the chicken embryo could regenerate rapidly after an injury, to make many new neurons." So he wondered if, "perhaps the same environment might stimulate [human] bone marrow stem cells to make neurons?"

    The Norwegian group tested that theory using fertilized chicken eggs. They first caused injury to the embryo's developing spinal cord. Then they introduced adult stem cells from human bone marrow into the affected area.

    Not only did these stem cells quickly develop into neurons to repair the site of injury, "we were able to show for the first time that these neurons were really functional," Glover said.

    "They had the right shape, they could generate nerve impulses, and they received contacts from other neurons," he said.

    The next step, according to Glover, will be experiments aimed at identifying exactly which compounds within this microenvironment are pushing adult stem cells to turn into neurons.

    "We speculate that a number of so-called neural growth factors, which are present in the chicken embryo spinal cord and presumably boost neuron formation during regeneration, are likely candidates," Glover said.

    According to Sanberg, the finding also suggests the lowly chicken might someday be a real lifesaver for humans stricken with spinal cord injury or degenerative brain diseases such as Multiple Sclerosis or Parkinson's.

    The pharmaceutical industry, for example, "already uses the chick embryo model to make vaccines and all sorts of things, because you can have a lot of these egg models in place, whereas rat models are much more expensive," Sanberg said. "So, as we try and understand how to make more neurons out of bone marrow, this is a very interesting model and one that could be ramped up commercially."

    However, the key finding remains the fact that adult stem cells can be pushed to develop into brain cells, given the right biochemical mix.

    "Bone marrow stem cells from adults are very attractive for this because they can be obtained easily, they are numerous, and they have already been studied and used in clinical treatments for blood and immune disorders for many years," Glover said.

    Use of adult stem cells would also get around ethical and moral issues that continue to dog the use of human embryonic stem cells -- although Glover stressed that, in many cases, embryonic stem cell research remains crucial.

    Nevertheless, he said, "if we can find out how to make neurons from bone marrow stem cells in a cell culture dish, we'd have a readily accessible source of neurons for brain repair."

    "This will take a lot of work," he added. "But at least now it seems possible."

    Source: Copyright © 2005 ScoutNews LLC. All rights reserved. (16/03/06)

    Adult stem cell research advances
    A laboratory rat unable to use its right front paw because of a spinal cord injury struggles to walk across a rope, loses its footing and falls.

    Then a rat that had the same injury scurries across the rope without a problem, just weeks after an injection containing adult stem cells from a human nose that were transformed into nerve cells.

    The rats are part of a line of research at the University of Louisville that could lead to treatments for spinal cord injuries, multiple sclerosis, Parkinson's disease and other nerve disorders.

    The rat's improvement after the injection is the second major discovery in the past few months at UofL that promises progress without using embryonic stem cells.

    In December, a research team at the James Graham Brown Cancer Center announced it had transformed stem cells from adult mice into brain, heart, nerve and pancreatic cells.

    The nasal stem-cell research - published most recently last week in the journal Stem Cells - involves using certain chemicals to direct the cells to become neurons, which send and receive messages between the nervous system and other parts of the body.

    "It amazes me still that we can take cells out of a human nose" and help an injured rat recover, said Fred Roisen, a neuroscientist who led the team. "I'm very optimistic."

    Experts said the research is unique.

    "This one has gone a lot further than the others," said Scott Whittemore, who is scientific director of UofL's Kentucky Spinal Cord Injury Research Center but is not on Roisen's research team. "This is a major step forward."

    Robert Miller, a professor of neuroscience at Case Western University in Cleveland, called the research "quite exciting." He said many studies have involved trying to make existing cells reconnect instead of introducing new neurons that promote recovery.

    The UofL researchers said clinical studies in humans could be anywhere from three to 10 years off, and any treatments wouldn't become widely available until after that. But some people who could benefit said they are hopeful.

    "This looks very promising," said Pam Kober, a 46-year-old Louisville resident with multiple sclerosis.

    Kober found out she had MS in 1999 after having headaches and numbness in her arms. Over the years, the illness has left her unable to drive at night, handle more than one household chore at a time or hold a full-time job.

    "Maybe in my lifetime they'll find something that will help," she said.

    The cells the team used came from the tissue that allows people to smell. Called the olfactory neurosensory epithelium, the tissue was taken from adults undergoing elective sinus surgery who volunteered for an endoscopic biopsy. The procedure doesn't harm the sense of smell.

    Researchers then used compounds to coax the cells into becoming neurons that attached to muscle tissue in the lab. The newly created cells can also produce myelin, a protective coating that insulates the nervous system.

    Source: Cincinatti Enquirer Copyright © 1995-2006 (16/03/06)

    Bone Marrow Transplantation Study Update: Participants Treated in Study to Stop MS Progression

    The Multiple Sclerosis Scientific Research Foundation is funding a multi-centre project to determine definitively whether transplanting bone marrow stem cells in people with MS can stop the disease. Led by Dr. Mark Freedman (MS neurologist) and Dr. Harold Atkins (bone marrow transplant physician), both at the University of Ottawa, the study involves 32 people with rapidly progressing multiple sclerosis who are likely to become severely disabled. Twenty-four of the participants will receive bone marrow transplantation while eight other people with the same kind of MS but who do not wish to have the procedure will be the control group. Recruitment began in October 2000. The MS Scientific Research Foundation is related to the MS Society of Canada, and receives most of its funding from the MS Society. This project is funded for $4 million over six years.

    As of January 2005, 17 people with MS are enrolled in the study. One person is in the control arm and has been followed for 34 months. Eleven people have received transplants to date and their follow up periods range from three to 39 months.

    Generally, the transplants have been well tolerated with mild or moderate side effects. At this point, there have been no documented MS relapses following the transplant procedure. There has been one death related to chemotherapy induced liver toxicity. The study was temporarily closed to recruitment from April 2003 to March 2004 to allow the safety committee to review the protocol. Modifications to the study protocol have been introduced to reduce the risk of liver toxicity.

    While the transplantation procedure has been done on people with MS in the US and several sites in Europe, this is the first time that the science behind the process is being scrutinized in such detail and with the involvement of a control group. The study also targets younger patients, earlier in their disease course, who may still have reversible disabilities, and it uses a different protocol.

    Bone marrow transplantation is used frequently to treat leukemia. In a very small number of people who have both MS and leukemia, it has been noted that their MS improved following the bone marrow stem cells transplant. This project should allow investigators to determine if bone marrow transplantation is an effective treatment in a group of closely matched people with MS, supporting the theories that the immune system is key to the disease. Equally important, should the procedure not fully stop the disease process, the researchers may be able to detect what triggers MS early on and discover how MS begins. They are monitored closely for any signs of disease activity in the participants at all stages of the procedure from enrolment to the end of study three years following their transplantation. Monitoring includes: complex immune system tests and tracking certain immune-related genetic changes in the hope of unveiling particular genes that might contribute to genetic susceptibility.

    The study is headed by Dr. Mark Freedman and Dr. Harold Atkins of The Ottawa Hospital and the University of Ottawa. Co-investigators include Dr. Jack Antel, Dr. Yves Lapierre, Dr. Amit Bar-Or and Dr. Douglas Arnold, Montreal Neurological Institute and McGill University; Dr. Pierre Laneuville, Royal Victoria Hospital and McGill University; Dr. Pierre Duquette, Notre-Dame Hospital and the University of Montreal; Dr. Rafick Sekaly, University of Montreal; Dr. Hans Messner, Princess Margaret Hospital and the University of Toronto; Dr. Paul O’Connor, St. Michael’s Hospital and the University of Toronto; Dr. Isabelle Bence-Bruckler and Dr. Lothar Huebsch, both at The Ottawa Hospital.

    A total of 24 people who have rapidly progressive MS will undergo bone marrow transplantation. A total of eight people with the same type of MS who decide not to participate in the study are serving as the control group.

    Inclusion criteria
    Participants will be invited to join the study on the basis of the following criteria:

    Between 18 and 50 years old Diagnosis of MS made by a neurology expert History of multiple early relapses within the first two years of disease Having reached Expanded Disability Status Scale (EDSS) of 3 or more within two years of diagnosis (moderate disability in one functional system; fully ambulatory) Having an EDSS score between 3 and 6 (intermittent or unilateral constant assistance required to walk 100m with or without resting) EDSS Cerebellar Functional subscore of 3 or more or EDSS Pyramidal Functional subscore of 3 or more (indicating at least partial paralysis of one side of the body [hemiparesis] or partial paralysis of the lower limbs [paraparesis] or moderate tremor of the arms, leg or trunk) MRI scan of the brain showing typical features of MS.

    The study is coordinated through the combined efforts of The Ottawa Hospital Blood and Marrow Transplant Program and the MS Research Clinic at The Ottawa Hospital. The study also involves the MS Clinic at St. Michael’s Hospital, Toronto, and the Bone Marrow Transplant Unit at the Princess Margaret Hospital, Toronto, as well as the MS Clinics at Notre-Dame Hospital and the Montreal Neurological Institute and the Bone Marrow Transplant Unit at the Royal Victoria Hospital, Montreal. Assessments for admission to the study will be carried out at the four clinics. Recruitment began in October 2000.

    Participants must be able to travel to and stay in one of the treatment centre areas (Ottawa or Montreal) for periods of time during the treatment procedure and be able to return periodically for monitoring. Yearly trips to Montreal for specialized MRI scanning will also be required for non-Montreal residents. The study coordinators will assist with these arrangements.

    Bone Marrow Transplantation Procedure
    The researchers are using what is known as autologous stem cell transplantation. They “harvest” a portion of each person’s own stem cells which will then be used to create a "new” immune system once they are transplanted back into the person. Powerful chemotherapy drugs are used to totally eliminate from the body the immune cells that are attacking the protective myelin coating of the central nervous system as well as removing any source of their replenishment.

    The following will take place, once a person meets the study criteria and agrees to take part in the study:

    Before receiving any treatment, participants will have an operation to remove bone marrow from their pelvis bones. It will be frozen and reserved in case it is needed to restore the immune system because of problems with regrowth of a new immune system.

    To obtain the stem cells needed to create the new immune system, participants will be given Cyclophosphamide, a chemotherapy drug, and a drug called G-CSF. It is a medication which causes the bone marrow to grow more white blood cells which then enter the bloodstream. About 11 and 12 days following the G-CSF injection, a portion of the white blood cells containing the stem cells will be collected from the bloodstream via leukophereis (a procedure similar to plasma exchange). These stem cells will be purified to remove any trace of the old immune cells before being frozen and reserved.

    Three drugs will then be given (Busulphan, Cyclophosphamide and antithymocyte globulin) over a period of several days to destroy the participants’ existing immune systems.

    Finally, the purified stem cells will be thawed and given back to each individual from whom they came in a procedure like a blood transfusion. The entire procedure will require participants to be hospital inpatients for several weeks.

    Risks and Side Effects
    The many potential risks and complications will be explained to each participant at several meetings before they have to decide about participating in the study. Great caution is being taken to ensure the health and safety of each treated participant, but each step of this treatment carries a risk of serious complications. These may be severe enough in a small percentage of patients to be fatal. A safety committee of experts in the field of bone marrow transplantation and MS will monitor all decisions about patient treatment for their protection. Participants in the study will be actively monitored for three years including medical examinations and periodic MRI scans.

    Some of the side effects of the treatment include back pain, muscle aches, fatigue, nausea, vomiting, diarrhea, dry mouth and temporary hair loss. More severe side effects may be serious infections and, rarely, a late life malignancy.

    Information about the Study
    For more information about the bone marrow transplantation study, please contact the principal study coordinator: Guylaine Théorêt,
    MS Research Clinic,
    The Ottawa Hospital,
    Phone: 613 737-8104, ext. 7;
    Fax: 613 737-8857
    or e-mail: [email protected] 

    MS Scientific Research Foundation
    The MS Scientific Research Foundation is related to the Multiple Sclerosis Society of Canada and receives most of its funding from the MS Society. While both organizations fund research, the MS Society also has an extensive services program for people with MS and their families. For more information, contact the MS Society at 1 800 268-7582 or visit our website.

    Source: Multiple Sclerosis Society of Canada © 2005 Multiple Sclerosis Society of Canada (22/02/06)

    New way to culture adult stem cells from bone marrow
    In a significant advance for regenerative medicine, researchers at Rice University have discovered a new way to culture adult stem cells from bone marrow such that the cells themselves produce a growth matrix that is rich in important biochemical growth factors.

    The research, which appears online in the Proceedings of the National Academy of Sciences, is notable not just because of the science - researchers found they could coax bone cells into produce up to 75 times more calcium - but also because the study was conducted by an undergraduate bioengineering senior, Niha Datta.

    "These results are important, not just because they hold great promise for regenerating healthy bone but also because they may be applicable to other tissues," said researcher Antonios Mikos, the John W. Cox Professor of Bioengineering and Director of Rice's Center for Excellence in Tissue Engineering. "This is also a notable personal achievement for Niha, because PNAS is one of the top scientific journals in the country and because this is the third peer-reviewed paper - and the second first-authored paper -- that she's produced in the past year."

    Tissue engineering, also known as regenerative medicine, involves harvesting stem cells from a patient's body and using them to grow new tissues that can be transplanted back into the patient without risk of rejection. Most tissue engineering approaches involve three components: the harvested adult stem cells, growth factors that cause the stem cells to differentiate into the right kind of tissue cells - like skin or bone - and a porous scaffold, or template, that allows the tissue to grow into the correct shape.

    "Finding the right combination of growth factors is always a challenge," Mikos said. "It's not unusual for adult stem cells to progress through a half-dozen or more stages of differentiation on their way to becoming the right tissue - and any missed cue will derail the process. In most cases, engineers have little choice but to take a trial-and-error approach to designing a growth-factor regime."

    In the study, Mikos's team hit upon the idea of having the stem cells create the proper growth medium themselves. The group, which included graduate student Quynh Pham and postdoctoral research associate Upma Sharma, accomplished this by seeding discs of titanium mesh with stem cells and encouraging them to form extracellular matrix, or ECM, the boney, calcified deposit that gives bone its structural strength.

    A comparison was then run on these pre-generated ECM constructs and on non-treated titanium scaffolds. The pre-treated surfaces encouraged calcification at a much faster rate. The researchers also found up to 75 times more calcium in the bone created by tissues in the pre-treated cultures.

    "To me, the most important element of the research is that it may one day contribute to new treatment options for patients," said Datta, who is planning to enter medical school in the fall. "One of the reasons I want to become a surgeon is so I can help bring cutting-edge work from the laboratory into clinical practice."

    Datta said one of the main reasons she chose to attend Rice was because of the tremendous opportunities available through Rice's Century Scholars Program. The program included funding for tuition as well as a chance to begin research in Mikos's lab during her freshman year.

    "My research experience at Rice has been life-changing in ways I could never have imagined four years ago," Datta said. "I never anticipated I would be traveling to international conferences, for example, but from the very beginning Dr. Mikos treated me as a valuable member of his research team. He provided encouragement. He let me follow my ideas. In short, he is the perfect mentor."

    Source: ©2005 News-Medical.Net (05/02/06)

    Study makes adult stem cells more usable
    The discovery of several new growth hormones has allowed American scientists to expand colonies of adult mouse stem cells, which usually don't grow in the laboratory, to volumes large enough for use in medical treatments.

    If the technology also works in human stem cells, researchers say, the technique would pave the way for a host of new therapies and research.

    Harvey Lodish, ChengCheng Zhang and their colleagues at the Whitehead Institute for Biomedical Research and MIT first tackled the problem six years ago. They published papers on their progress in 2003 and 2005, and the new discoveries build on this previous work.

    Their latest report can be found in a January online issue of Nature Medicine.

    Stem cells from early embryos can be transferred to the laboratory, grown into thriving colonies of basic cells, and can be programmed into becoming any type of cell from neural tissue to bones, blood or organs.

    On the other hand, when the rare stem cells that can be found in adults are placed in Petri dishes, they refuse to grow and quickly differentiate into adult tissue identical to the organs from which they came.

    Developing stem cells from a person's own body is an alternative to using embryonic tissue, but it hasn't been a very viable option up until now because of the expansion problem.

    Lodish and his team approached the issue from a highly common sense point of view.

    "My colleague Zhang made a fundamental conceptual breakthrough," Lodish told UPI. "He suggested starting by recreating the environment in which stem cell growth normally occurs and identifying what elements in that environment are unique. His approach worked."

    He explained,"We discovered several new growth factors produced by blood stromal cells, or supportive cells, in mouse embryos that help mouse blood stem cells from bone marrow multiply, and when we added the growth factors to the culture medium in which we grew blood-forming (hematopoietic) adult stem cells, the cells multiplied thirtyfold."

    "The most we were able to produce before was an eightfold increase, which is not enough for treatments like bone marrow transplants and gene therapy, or even for research," he noted.

    Lodish said that the new growth factors were called angiopoietin-like hormones. They had already been discovered but not explored, which gave them "orphan" status.

    When the team added them to the culture medium along with IGF-2, thrombopoietin, stem cell factor and fibroblast growth factor - known growth-promoting hormones also found in the natural embryonic environment - the adult stem cells grew.

    The team also discovered that all the growth factors needed to be present before expansion would occur.

    "None of these hormones produced a significant effect by itself, it took all of them working together. That was why Zhang's approach was so important: we got the total picture right away," Lodish said.

    "This is an exciting and important first step in expanding the research and therapeutic applications of hematopoietic stem cells," said James Batty, Jr., Chair of the Stem Cell Task Force at the National Institutes of Health, in an interview with UPI. "I'm quite confident that Dr. Lodish and others will build on these protocols to establish even better growth-promoting regimens in the future."

    While the team's pioneering work was done in mice, they are now collaborating with researchers in Lund, Sweden to identify growth factors in human cord blood that support the development of human hematopoietic stem cells. Lodish said that, after the growth factors have been discovered, recombinant DNA technologies will be used to bioengineer cells that can produce the growth factors in enough quantity for therapy and research.

    "The human body makes several hundred hormone-like proteins like the growth factors we discovered, and we have only identified the function of a hundred or so," said Lodish. "They are all there waiting for us, we just have to find them and discover their function."

    Source: United Press International © Copyright 2006 United Press International, Inc. All Rights Reserved (30/01/06)

    Key bone marrow cells hide at edges, study finds
    Scientists have found blood stem cells hiding out in the edges of bone marrow, and said on Monday their finding could help ease lifesaving stem cell transplants for diseases such as cancer.

    They invented a technique that makes it possible to see a stem cell alive in bone marrow -- something never done before.

    Scientists usually find the powerful but elusive cells by looking for proteins called markers that are active on the stem cells' surfaces.

    The cells are not clustered throughout bone marrow, as had been thought, but live alongside bone-forming cells on the edges of the marrow, the team at the University of Michigan Medical School and University of Tsukuba in Japan wrote in the Proceedings of the National Academy of Sciences.

    This might make transplants easier, said Dr. Doug Engel, who worked on the study. Currently doctors must remove large amounts of bone marrow from a donor and separate stem cells, which are infused into a sick patient.

    "Maybe we can find a way to expand the stem cell population in the niche," Engel said in a telephone interview.

    "Then perhaps we can make human bone marrow harvests less invasive and less painful."

    Where the stem cells live might hold a key to their abilities to create all the different types of blood cells, Engel said.


    To find the stem cells, Norio Suzuki and colleagues at the University of Tsukuba spliced a green fluorescent protein gene from jellyfish into two genes uniquely used by the blood stem cells, one called Gata-2, and a gene called IS that helps control Gata-2.

    This made the stem cells glow under ultraviolet light. "We made a whole mouse that would express green fluorescent protein under the control of the Gata-2 gene promotor," Engel said.

    "We took time-lapse movies of frozen sections from mouse leg bone as seen under a fluorescent microscope," Engel added.

    "They clearly show individual, isolated hematopoietic stem cells at the edge of the bone marrow."

    When bone marrow stem cells, called hematopoietic stem cells, are transplanted, they proliferate, giving rise to immune cells and various other blood cells.

    Scientists had presumed they circulated throughout the bone marrow. In fact, they sat still and in contact with osteoblasts -- bone-forming cells.

    In a second study in the same journal, another team of scientists said they found another unusual source of support for stem cells -- prion proteins.

    Prions are perhaps best known as the agents that, when misshapen, cause mad cow disease and related diseases. Mad cow disease, known scientifically as bovine spongiform encephalopathy, and similar diseases destroy the brains of other animals and humans.

    Prions have a normal function too -- but nobody knows what it is.

    Susan Lindquist of the Massachusetts Institute of Technology and colleagues found prion protein expressed, or active, in bone marrow stem cells. She said that means prions probably help blood stem cells during the transplant process and might serve as a marker to help find them.

    Source: Reuters Alertnet (30/01/06)

    Role of the Nervous System in Regulating Stem Cells Discovered
    Study led by Mount Sinai School of Medicine may provide new hope for cancer patients and others with compromised immune systems

    New study by Mount Sinai researchers may lead to improved stem cell therapies for patients with compromised immune systems due to intensive cancer therapy or autoimmune disease. The study is published in this week’s issue of Cell.

    A group, led by Paul Frenette, MD, Associate Professor of Medicine at Mount Sinai School of Medicine, found that the sympathetic—or “fight or flight” branch—of the nervous system plays a critical role in coaxing bone marrow stem cells into the bloodstream. Bone marrow cells known as hematopoietic stem cells are the source for blood and immune cells.

    Hematopoietic stem cell transplants are now routinely used to restore the immune systems of patients after intensive cancer therapy and for treatment of other disorders of the blood and immune system, according to the National Institutes of Health. While physicians once retrieved the stem cells directly from bone marrow, doctors now prefer to harvest donor cells that have been mobilized into circulating blood.

    In normal individuals, the continuous trafficking of the stem cells between the bone marrow and blood fills empty or damaged niches and contributes to the maintenance of normal blood cell formation, according to the researchers. Although it has been known for many years that the mobilization of hematopoietic stem cells can be enhanced by multiple chemicals, the mechanisms that regulate this critical process are largely unknown, they said.

    One factor in particular, known as hematopoietic cytokine granulocyte-colony stimulating factor (G-CSF), is widely used clinically to elicit hematopoietic stem cell mobilization for life-saving bone marrow transplantation, said Dr. Frenette.

    Several years ago, Dr. Frenette’s group reported that a second compound, fucoidan, which is synthesized by certain seaweeds, could also spur the stem cells into action. The group speculated that the seaweed derivative might work by imitating a similar compound, called sulfatide, naturally present in mammalian tissues.

    To test the idea, the researchers examined mice lacking the enzyme responsible for making sulfatide.

    “Lo and behold, mice lacking the enzyme Cgt did not mobilize hematopoietic stem cells at all when treated with the stimulating factor G-CSF or fucoidan,” Dr. Frenette said. “You don’t get such dramatic results that often in science. We knew we had stumbled onto something important.”

    To their surprise, further study failed to connect the stalled stem cell movement to sulfatide. Rather, they found, the deficiency stemmed from a defect in the transmission of signals sent via the sympathetic nervous system. The products of Cgt contribute to the myelin sheath that coats and protects nerve cells, they explained.

    Mice with other nervous system defects also exhibited a failure to mobilize bone marrow stem cells, they found. Moreover, drugs that stimulate the sympathetic nervous system restored stem cell movement into the blood stream in mice with an impaired ability to respond to norepinephrine, the signature chemical messenger of the sympathetic system.

    “The nervous system plays an important role in producing signals that maintain the stem cell niche and retention in bone marrow,” Dr. Frenette said.

    “The new findings add another dimension of complexity to the processes involved in stem cell maintenance and mobilization and emphasize the interrelationships among the nervous, skeletal and hematopoietic systems,” he added. “They all have to work together – to talk to each other – to produce blood and maintain stem cells.”

    The results suggest that differences in the sympathetic nervous systems of stem cell donors may explain “conspicuous variability” in the efficiency with which they mobilize hematopoietic cells into the bloodstream, the researchers said. Furthermore, drugs that alter the signals transmitted by the sympathetic nervous system to the stem cells in bone may offer a novel strategy to improve stem cell harvests for stem cell-based therapeutics, they added.

    The unexpected findings by Frenette and his colleagues further “suggest that the pharmacological manipulation of the sympathetic nervous system may be a means of therapeutically targeting the stem cells in their niche for the purpose of either mobilization or, conversely, attracting stem cells to the niche following transplantation,” they added.

    Source: Newswise © 2006 Newswise (27/01/06)

    BrainStorm Files Patent Application for Stem Cell Procedure With Potential for Multiple Sclerosis Therapy

    BrainStorm Cell Therapeutics, the developer of NurOwn(tm) bone marrow derived stem cell therapeutic products for the treatment of neurodegenerative diseases, announced today that a patent application has been filed with the U.S. Patent and Trademark Office for a new procedure to derive oligodendrocyte-like cells. The invention involves inducing oligodendrocyte-like cells using the company's proprietary bone marrow derived human mesenchymal stem cell technology.

    The patent application was filed by the technology transfer company of Tel Aviv University, Ramot, on the basis of research funded by Brainstorm. Worldwide rights to the development and commercialization of the new technology are exclusively licensed to BrainStorm.

    "Developing the capability to derive oligodendrocyte-like cells is a major step forward because of the important role that oligodendrocyte cells are believed to have in restoring cell function in patients suffering from Multiple Sclerosis and other demyelinating diseases,'' said Yoram Drucker, Principal Executive Officer of BrainStorm.

    "Now that we have demonstrated that mesenchymal stem cells can be induced to differentiate in vitro to oligodendrocyte lineage and form functional cells, our next goal will be to test the oligodendrocyte-like cells in animal models of Multiple Sclerosis,'' said Dr. Daniel Offen, BrainStorm's Chief Scientist.

    Brainstorm's success in deriving olgodendrocyte-like cells follows several other major technological achievements made by the company during the past year using the company's proprietary bone marrow derived stem cell technology.

    In other studies, Brainstorm successfully used bone marrow stem cells to produce dopaminergic-like cells shown to be capable of dopamine secretion and to benefit animal models of Parkinson's disease.

    Brainstorm also used its bone marrow stem cell technology to produce astrocyte-like cells with the capacity of producing glial derived neurotrophic factor (GDNF), the most potent neurotrophic factor known for dopaminergic neurons. Transplanted dopamine- and GDNF producing-cells, acting on their own or in combination, hold great promise for replacement and preservation of neurons in Parkinson's and other neurodegenerative diseases.

    About BrainStorm Cell Therapeutics Inc.

    BrainStorm Cell Therapeutics Inc. is an emerging company developing neural-like stem cell therapeutic products, NurOwn(tm), based on autologous bone marrow derived stromal cells, for treatment of neurodegenerative diseases. NurOwn(tm) patent-pending technology is based on discoveries made by the team of prominent neurologist, Prof. Eldad Melamed, Head of Neurology at Rabin Medical Center, and expert cell biologist Dr. Daniel Offen, at the Felsenstein Medical Research Center of Tel-Aviv University, enabling the differentiation of bone marrow derived stem cells into functional neurons and astrocytes, as demonstrated in animal models. The company holds rights to develop and commercialize the technology through an exclusive, worldwide licensing agreement with Ramot at Tel Aviv University Ltd., the technology transfer company of Tel Aviv University. The company's initial focus is on developing treatments for Parkinson's Disease.

    About Stem Cell Therapy

    Stem cells are non-specialized cells with a remarkable potential for both self-renewal and differentiation into cell types with a specialized function, such as muscle, blood or brain cells. Stem cells may be sourced from fetal or embryonic tissue or from adult tissue reservoirs such as bone marrow. Use of embryonic stem cells, has become the center of significant ethical and moral debate. In contrast, use of adult stem cells does not face the same moral or legal controversy. Stem cell therapy aims to ``cure'' disease by replacing the 'diseased' cells with 'healthy' cells derived from stem cells. This approach has the potential to revolutionize medicine and, if successful, the implied commercial opportunities are great. Currently, both embryonic stem cells (ESC) and adult stem cells (ASC) are being explored as the potential basis for multiple cell therapy products.

    Source: BrainStorm Cell Therapeutics (26/01/06)

    Banking on Stem Cells

    A REVOLUTIONARY therapy developed in Melbourne promises to become the ultimate health insurance for people with heart disease, bone problems, arthritis and those needing a hip replacement

    Biotech firm Mesoblast is setting up a "stem cell bank" where donors can deposit healthy bone marrow to be used later to repair bones and tissue and treat disease.

    If human clinical trials about to start in Melbourne and Sydney are successful, the revolutionary treatment could:

    • Offer a treatment for the repair of heart muscles in chronic heart disease.
    • Replace expensive and painful hip- replacement surgery.
    • End long waiting lists for some elective surgeries.
    • Offer longer-lasting treatments for arthritis.
    • Save millions in health-care dollars, and
    • Help athletes recover from injuries more quickly.

    The therapy isolates special adult stem cells from bone marrow, multiplying them to produce new tissue. (16/01/06)

    Molecule dictates how stem cells travel

    U.S. researchers have defined a molecule that dictates how blood stem cells travel to the bone marrow and establish blood and immune cell production.

    The discovery by researchers at the Massachusetts General Hospital Center for Regenerative Medicine and the Harvard Stem Cell Institute may help improve bone marrow stem cell transplantation and the treatment of several blood disorders.

    "This is another remarkable example of how bone and bone marrow interact. A receptor known to participate in the body's regulation of calcium and bone also is critical for stem cells to engraft in the bone marrow and regenerate blood and immune cells," says Dr. David Scadden, director of the MGH Center for Regenerative Medicine and co-director of the HSCI.

    "It reminds us how tissues interact and how looking closely at where stem cells reside may tell us a lot about how to manipulate them."

    The findings will be published in the journal Nature.

    Copyright 2006 by United Press International. All Rights Reserved.(13/01/06)

    By Beezy Marsh, Health Correspondent

    Scientists are predicting a "cure" for arthritis within the next decade after they successfully grew human cartilage from a patients' own stem cells for the first time.

    The breakthrough paves the way for cartilage transplant operations for more than two million people who suffer the most severe form of the bone disease, osteoarthritis, which leaves them unable to walk and in constant pain.

    Experts from the University of Bristol took just over a month to grow a half-inch piece of cartilage using stem cells, which are self-renewing and have the ability to grow into blood, bones or organs.

    The cells were taken from the bone marrow of pensioners undergoing National Health Service replacement surgery due to the disease.

    Crucially, the new technique is expected to overcome problems of transplant rejection because the patient's own cells would be used to create the cartilage. This would also avoid the ethical concerns over the use of human embryos in stem cell research. The most potent stem cells are found in human embryos, but a lesser supply can also be found in adult bone marrow....

    Source: news.telegraph

    For more on this story please click the link above. (17/12/05)

    Adult stem cells 'fusion hope'
    Scientists believe adult stem cells may be more flexible than first thought.

    Embryonic stem cells can become any tissue, but adult ones are limited to the part of the body they are in.

    US researchers said evidence had shown adult cells could be effectively fused with other cells to work elsewhere, New Scientist magazine reported.

     The Oregon Health and Science University team said it meant adult stem cells may be useful in fighting disease, but UK experts were less sure.

    Critics of embryonic stem cell research have argued it is not ethical to create human embryos for stem cells only to destroy them.

    As a result scientists - particularly in the US where state funds cannot be used to fund embryonic stem cell research - have been exploring ways of treating disease with stem cells via adult cells.

    Previous research has shown that adult cells can be fused with cells from other parts of the body.

    But because the fused cells contain twice the number of chromosomes they have trouble dividing, and struggle to replenish damaged tissue.

    Markus Grompe, who led the Oregon team, told the American Society for Cell Biology this week that he had evidence that fused cells could reduce the number of chromosomes to the normal number.

    He said the process was called "reduction divisions" and occurred routinely.

    The theory is that cells are pre-programmed to know how many chromosomes they have, and can reduce their number if they have too many.

    The researchers have shown that mice with a disease called tyrosinemia type 1, which causes jaundice and cirrhosis of the liver, can be cured by infusing their livers with bone marrow stem cells.

    Analysis suggested the cells had reverted to the right number of chromosomes - the first time this had been seen outside of insects.

    However, why this happened was not clear.

    Dr Grompe is now investigating whether it is possible to use a signalling molecule called insulin-like growth factor 1 to speed up the process, as it is too slow to be effective on many human conditions.


    Arnold Kriegstein, who heads the Institute for Stem Cell and Tissue Biology at the University of California, said: "In much of the stem cell field, the promise is way down the line.

    "But this is something that has already shown potential."

    But Stephen Minger, director of the Stem Cell Biology Laboratory at King's College London, said fusion had limited potential.

    "There are few stem cells that can fuse like this, bone marrow stem cells are one.

    "But I am not sure how useful it is to spend time on this, when other sources such as embryonic stem cells have the potential for much more.

    "It has to be remembered this is coming out of the US, there is a political agenda."

    Source: BBC News Online (15/12/05)

    © Multiple Sclerosis Resource Centre

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