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Because neurons (nerve cells) in the central nervous system (the brain and spinal cord) do not repair or replace themselves after being injured, researchers are investigating whether transplanting cells into an injured area can restore function.

One of the many challenges for researchers is obtaining cells that will function as neurons in the brain or spinal cord. Because a persons body doesnt have spare neurons for transplantation, efforts are being made to find other cells that can be transformed into neurons. One potential source is stem cells from human embryos. Less than a week after conception cells in an embryo begin to differentiate that is, they begin to form specific types of cells, such as bone cells, red blood cells, heart muscle cells, and so on. Stem cells are simply cells that can differentiate into other types of cells. Early in the life of an embryo stem cells have the potential to differentiate into the more than two hundred types of cells in a human body. There are other kinds of stem cells, including stem cells in adults, which can differentiate into a more limited number of types of cells.

Using embryonic stem cells for transplantation is controversial because it is necessary to first create human embryos to produce the stem cells and then kill the embryos in the process of harvesting the stem cells. Opponents of the process contend that it is unethical or immoral to create and then kill any form of human life for the purpose of harvesting stem cells. Proponents of stem cell transplantation either claim that embryos created in a laboratory have no value or significance apart from producing stem cells or that the end of helping injured or ill people justifies the means of creating and then killing human life.

Apart from the controversy about creating and killing human embryos, stem cell researchers are faced with another challenge which is partly practical and partly ethical. The bodys immune system recognizes what is part of the body and what is not. Every cell in the body has protein molecules on the surface of the cell wall that identify the cell as being part of the body (these are known as human leukocyte antigens (HLA)). These markers are recognized by the cells in our immune systems. If the immune system doesnt detect the bodys specific markers, it will sound the alarm and go on the attack. This allows our immune system to recognize and fight invaders in the form of bacteria, viruses, and fungi, protecting us from diseases that would otherwise kill us.

However, this same ability of the immune system presents a serious problem when tissue from another person (or animal) is transplanted into the body. The immune system will ordinarily identify the transplant as foreign and begin to attack it. The attack is carried out by cells using chemical weapons that can kill other cells. This process is known as transplant rejection.

To prevent rejection two different strategies have been used. One is to find a transplant donor who has genetic markers (HLA) that are similar to those of the person receiving the transplant. The more similar the markers, the less likely it is that the immune system will reject the transplant. The other strategy is to administer drugs to transplant recipients that suppress the ability of the immune system to recognize and target transplants for destruction. While these drugs usually work, they have numerous side-effects and can make an individual more vulnerable to infections. Often times both strategies are used.

One potential solution to the problem of transplant rejection would be to create a transplant with markers identical to those of the person receiving the transplant. A persons DNA contains the unique blueprint for that persons body, including the details for the markers (HLA) that are recognized by the immune system. Some researchers are attempting to insert human DNA into cells that are then used to create human embryos. This process is known as cloning that is, artificially producing another organism with DNA that is identical to the DNA of the donor. Cloning has been performed with some types of animals but not with a human being(1). If human cloning is eventually successful, the clone would have markers identical to those of the DNA donor. This would potentially allow transplants to be created with the DNA of the patient, which would be recognized by the immune system as belonging to the body. There would be no potential for transplant rejection and no need for drugs to suppress the immune system.

However, even if cloning is successful, researchers will still need to learn how to stimulate an embryonic stem cell to produce a neuron rather than a skin cell or some other type of cell. Transplanting undifferentiated stem cells runs the risk of creating a tumor, an event which has actually occurred when embryonic stem cells have been transplanted into mice. Furthermore, while finding a source of cells that can differentiate into neurons is one major challenge in developing a cure for spinal cord injuries, there are others (click on the Treatments for the Future link under the Spinal Injury Treatment tab.) Consequently, any effective treatment to repair spinal cord injuries using embryonic stem cells lies years, if not a decade or more, in the future.

Cloning is one example of genetic engineering, an activity in which people manipulate DNA to create organisms that wouldnt otherwise exist in nature. While the first mammal (Dolly the sheep) was cloned in 1997, some clones have had health problems not characteristic of the species (including Dolly), are more prone to have offspring with birth defects, or have much shorter than normal life spans. The long term results of cloning are not known. As a result, ethical issues abound, and particularly when human cloning is the issue.

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Stem Cell Research in pursuit of Spinal Cord Injury ...

Research from Karolinska Institutet in Sweden suggests that the expression of the so called MYC gene is important and necessary for neurogenesis in the spinal cord. The findings are being published in the journal EMBO Reports.

The MYC gene encodes the protein with the same name, and has an important role in many cellular processes such as proliferation, metabolism, cell death and the potential of differentiation from immature stem cells to different types of specialized cells. Importantly it is also one of the most frequently activated genes in human cancer.

Previously MYC has been shown to promote proliferation and inhibit differentiation in dissociated cells in culture. However, in the current study researchers demonstrate that in the intact neural tissue from chickens, MYC promotes differentiation of neural cells rather than their proliferation.

"We hope that this news knowledge can be important for developing future strategies to promote nerve cell development, for example in patients with spinal cord injuries," says principal investigator Marie Arsenian Henriksson, professor at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet.

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New findings on neurogenesis in spinal cord

14 hours ago This image shows an embryonic stem cell differentiating into a neuronal cell. Credit: Anne Rupprecht/Vetmeduni Vienna

Cells have a metabolism that can be altered according to its function. If cellular metabolism is disturbed, it can lead to disease of the entire organism. Researchers at the Vetmeduni Vienna discovered that the uncoupling proteins UCP2 and UPC4 are involved in different types of cellular metabolism. As a result, cell alterations can now be detected much earlier than was thus far possible. This research work was recently published in the PLOS ONE journal.

UCPs or uncoupling proteins are present in mitochondria, the powerhouse of each cell in the body. The functions of most of the five known UCPs remain mysterious (UCP2-UCP5), whereby only the distinct function for UCP1 has thus far been discovered. UCP1 is responsible for heat production when muscle activity is deficient such as is the case with babies and animals in hibernation. The research team at the Department of Physiology and Biophysics at the University of Veterinary Medicine in Vienna were able to provide a fundamental explanatory concept for the function of UCP2 and UPC4 for the first time. Each of these proteins are involved in different types of cell metabolism.

UCP2 in Stem Cells and Cancer Cells

In earlier studies of immune cells, lead author, Anne Rupprecht, had already shown that UCP2 could be involved in increased metabolism. Embryonic stem cells precisely exhibit such an increased metabolism, as they rapidly and continually divide, just like cancer cells. Rupprecht searched for various UCPs in embryonic stem cells of mice and in effect found UCP2. "Very high amounts of UCP2 even indicated an especially strong increase in metabolism. In other studies UCP2 had also already been detected in cancer cells", according to Rupprecht.

UCP4 in Nerve Cells

In contrast to UCP2, UCP4 is only found in nerve cells. Nerve cells have a completely different metabolism. They seldom divide, unlike stem cells and cancer cells. The research team of Prof. Elena Pohl therefore examined embryonic stem cells that differentiated to nerve cells in culture. On the basis of this model system, the researchers could show that UCP2 is still existent in the quickly reproducing stem cells, yet at the moment of differentiation are replaced by UPC4.

"In our work, we have examined the natural process of cell differentiation from stem cells to neurons. We know that metabolism changes during differentiation. The fact that we found UCP2 in one case and in the other UCP4 proves for the first time that these proteins are associated with varying types of cell metabolism", specified Elena Pohl.

The researchers, for example, found only UCP2 in neuroblastoma cells - nerve cells that have malignant changes. UCP4, the usual protein of nerve cells was not detectable. UPC4 apparently got lost in the changed nerve cells that were on their way to becoming rapidly reproductive cancer cells.

UCPs for early detection of disease

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Hot on the trail of cellular metabolism: Researchers unravel the function of cell proteins

They used a process similar to one they used in an earlier project published last September where they reported creating neural networks in the brains of mice. In both cases the researchers reprogrammed the nerve support cells known as astrocytes into functional nerves. Astrocytes tend to be abundant, particularly at the site of injury where they proliferate and form scar tissue that actually prevents regrowth of the damaged nerves.

The Texas teams first step involved using a biologic substance to manipulate the expression of genes in the astrocytes at the site of spinal injury in the mice. They tried 12 different ones before they found one that is efficient in turning the protective cells into progenitor cells for nerves; think of them as middlemen between nerve stem cells and adult nerve. They then used a common drug called valproic acid to encourage those progenitor cells to mature into functioning nerves.

The work seems to map out a strategy to get new nerve growth directly in patients, or in vivo. The paper was published in Nature Communication and a press release from the university was picked up by ScienceCodex and it quoted the senior researcher Chun-Li Zhang on the impact:

You can read about some of CIRMs dozens of projects trying to repair or regrow nerve cells in our stem cells and stroke fact sheet.

Don Gibbons

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CIRM Stem Cell Research Updates: Team tricked scar tissue ...

The video begins like a clip from a James Bond movie, where the billionaire tycoon announces his plan to save humanity.

"Since the dawn of time, great men have challenged the status quo and dared to dream," an off-screen female narrator says in a sultry British accent while images of Leonardo da Vinci, Martin Luther King and other great historical figures parade across the screen.

The great man in question is none other than Peter Nygrd, the Helsinki-born, Manitoba-raised fashion magnate best known as the founder of Nygrd International.

And his plan to save humanity? Use stem-cell research to cure diseases and live forever, just as you would expect a billionaire tycoon to declare in a Bond movie.

In a 10-minute YouTube video titled Bahamas Stem Cell Laws: The Peter Nygrd Breakthrough, the 70-year-old former Winnipegger claims to be at the forefront of scientific and legislative efforts to further the achievements of stem-cell research.

Nygrd claims to have lobbied the Bahamian government to further stem-cell research, though the Bahamas Weekly reported the island nation's attorney general denied the billionaire was involved in drafting legislation.

That alone is fascinating, but Nygrd isn't just a stem-cell advocate. He says he's personally involved in the research by receiving injections of his own cells grown in Peter, or rather, petri dishes.

Yes, Nygrd claims he is actually getting younger. In his video, he calls stem-cell research a game-changer for humanity.

"This could eliminate all disease. This perhaps is immortality," he breathlessly states in a video that appears entirely serious.

"Ponce de Leon had the right idea. He was just too early," Nygrd continues, referring to the 16th-century conquistador who searched for the fountain of youth. "That was then. This is now."

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Nygrd uses stem cells to pursue immortality

UT Southwestern Medical Center researchers created new nerve cells in the brains and spinal cords of living mammals without the need for stem cell transplants to replenish lost cells.

Although the research indicates it may someday be possible to regenerate neurons from the body's own cells to repair traumatic brain injury or spinal cord damage or to treat conditions such as Alzheimer's disease, the researchers stressed that it is too soon to know whether the neurons created in these initial studies resulted in any functional improvements, a goal for future research.

Spinal cord injuries can lead to an irreversible loss of neurons, and along with scarring, can ultimately lead to impaired motor and sensory functions. Scientists are hopeful that regenerating cells can be an avenue to repair damage, but adult spinal cords have limited ability to produce new neurons. Biomedical scientists have transplanted stem cells to replace neurons, but have faced other hurdles, underscoring the need for new methods of replenishing lost cells.

Scientists in UT Southwestern's Department of Molecular Biology first successfully turned astrocytes -- the most common non-neuronal brain cells -- into neurons that formed networks in mice. They now successfully turned scar-forming astrocytes in the spinal cords of adult mice into neurons. The latest findings are published today in Nature Communications and follow previous findings published in Nature Cell Biology.

"Our earlier work was the first to clearly show in vivo (in a living animal) that mature astrocytes can be reprogrammed to become functional neurons without the need of cell transplantation. The current study did something similar in the spine, turning scar-forming astrocytes into progenitor cells called neuroblasts that regenerated into neurons," said Dr. Chun-Li Zhang, assistant professor of molecular biology at UT Southwestern and senior author of both studies.

"Astrocytes are abundant and widely distributed both in the brain and in the spinal cord. In response to injury, these cells proliferate and contribute to scar formation. Once a scar has formed, it seals the injured area and creates a mechanical and biochemical barrier to neural regeneration," Dr. Zhang explained. "Our results indicate that the astrocytes may be ideal targets for in vivo reprogramming."

The scientists' two-step approach first introduces a biological substance that regulates the expression of genes, called a transcription factor, into areas of the brain or spinal cord where that factor is not highly expressed in adult mice. Of 12 transcription factors tested, only SOX2 switched fully differentiated, adult astrocytes to an earlier neuronal precursor, or neuroblast, stage of development, Dr. Zhang said.

In the second step, the researchers gave the mice a drug called valproic acid (VPA) that encouraged the survival of the neuroblasts and their maturation (differentiation) into neurons. VPA has been used to treat epilepsy for more than half a century and also is prescribed to treat bipolar disorder and to prevent migraine headaches, he said.

The current study reports neurogenesis (neuron creation) occurred in the spinal cords of both adult and aged (over one-year old) mice of both sexes, although the response was much weaker in the aged mice, Dr. Zhang said. Researchers now are searching for ways to boost the number and speed of neuron creation. Neuroblasts took four weeks to form and eight weeks to mature into neurons, slower than neurogenesis reported in lab dish experiments, so researchers plan to conduct experiments to determine if the slower pace helps the newly generated neurons properly integrate into their environment.

In the spinal cord study, SOX2-induced mature neurons created from reprogramming of astrocytes persisted for 210 days after the start of the experiment, the longest time the researchers examined, he added.

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New neurons generated in brains, spinal cords of living adult mammals

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Newswise DALLAS, Feb. 25, 2014 UTSouthwestern Medical Center researchers created new nerve cells in the brains and spinal cords of living mammals without the need for stem cell transplants to replenish lost cells.

Although the research indicates it may someday be possible to regenerate neurons from the bodys own cells to repair traumatic brain injury or spinal cord damage or to treat conditions such as Alzheimers disease, the researchers stressed that it is too soon to know whether the neurons created in these initial studies resulted in any functional improvements, a goal for future research.

Spinal cord injuries can lead to an irreversible loss of neurons, and along with scarring, can ultimately lead to impaired motor and sensory functions. Scientists are hopeful that regenerating cells can be an avenue to repair damage, but adult spinal cords have limited ability to produce new neurons. Biomedical scientists have transplanted stem cells to replace neurons, but have faced other hurdles, underscoring the need for new methods of replenishing lost cells.

Scientists in UTSouthwesterns Department of Molecular Biology first successfully turned astrocytes the most common non-neuronal brain cells into neurons that formed networks in mice. They now successfully turned scar-forming astrocytes in the spinal cords of adult mice into neurons. The latest findings are published today in Nature Communications and follow previous findings published in Nature Cell Biology.

Our earlier work was the first to clearly show in vivo (in a living animal) that mature astrocytes can be reprogrammed to become functional neurons without the need of cell transplantation. The current study did something similar in the spine, turning scar-forming astrocytes into progenitor cells called neuroblasts that regenerated into neurons, said Dr. Chun-Li Zhang, assistant professor of molecular biology at UTSouthwestern and senior author of both studies.

Astrocytes are abundant and widely distributed both in the brain and in the spinal cord. In response to injury, these cells proliferate and contribute to scar formation. Once a scar has formed, it seals the injured area and creates a mechanical and biochemical barrier to neural regeneration, Dr. Zhang explained. Our results indicate that the astrocytes may be ideal targets for in vivo reprogramming.

The scientists' two-step approach first introduces a biological substance that regulates the expression of genes, called a transcription factor, into areas of the brain or spinal cord where that factor is not highly expressed in adult mice. Of 12 transcription factors tested, only SOX2 switched fully differentiated, adult astrocytes to an earlier neuronal precursor, or neuroblast, stage of development, Dr. Zhang said.

In the second step, the researchers gave the mice a drug called valproic acid (VPA) that encouraged the survival of the neuroblasts and their maturation (differentiation) into neurons. VPA has been used to treat epilepsy for more than half a century and also is prescribed to treat bipolar disorder and to prevent migraine headaches, he said.

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Researchers Generate New Neurons in Brains, Spinal Cords of Living Adult Mammals Without the Need of Stem Cell ...

REGINA Meeting Rick Hansen during his Man in Motion world tour sparked six-year-old Josef Buttigiegs fascination with biology and set his career course in motion.

Twenty-eight years after first meeting Hansen, Buttigieg is a biology professor at the University of Regina. Recently he received a $100,000 grant over two years from the Saskatchewan Health Research Foundation (SHRF) to improve the lives of people with spinal cord injuries.

One day Buttigieg hopes hes able to heal his hero.

He vividly recalls hearing Hansen speak at his elementary school in Toronto and talking with him afterwards.

I was really curious about how being in a car accident can result in a spinal cord injury or not being able to walk I just couldnt fathom that, Buttigieg said.

During his first year at McMaster University in Hamilton, Buttigieg again crossed paths with Hansen when he spoke at the university during a ceremony where he received an honorary doctorate.

Further inspired, Buttigieg became a volunteer research student in a spinal cord injury lab at McMaster before pursuing graduate studies there. He went on to work with a prominent neurosurgeon specializing in spinal cord injuries before arriving at the U of R in 2011 and starting his research program.

One of the focuses of Buttigiegs research is stem cell regeneration for spinal cord injuries, stroke and multiple sclerosis.

In terms of the damage to the nervous system, its very similar between the three cases, he said.

When a spinal cord is healthy, a signal is sent from the brain to the nerve, and then the nerve is turned off.

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Helping people with spinal cord injuries

A new study describes the complexity of the new T cell repertoire following immune-depleting therapy to treat multiple sclerosis, improving our understanding of immune tolerance and clinical outcomes.

In the Immune Tolerance Network's (ITN) HALT-MS study, 24 patients with relapsing, remitting multiple sclerosis received high-dose immunosuppression followed by a transplant of their own stem cells, called an autologous stem cell transplant, to potentially reprogram the immune system so that it stops attacking the brain and spinal cord. Data published in the Journal of Clinical Investigation quantified and characterized T cell populations following this aggressive regimen to understand how the reconstituting immune system is related to patient outcomes.

ITN investigators used a high-throughput, deep-sequencing technology (Adaptive Biotechnologies, ImmunoSEQTM Platform) to analyze the T cell receptor (TCR) sequences in CD4+ and CD8+ cells to compare the repertoire at baseline pre-transplant, two months post-transplant and 12 months post-transplant.

Using this approach, alongside conventional flow cytometry, the investigators found that CD4+ and CD8+ lymphocytes exhibit different reconstitution patterns following transplantation. The scientists observed that the dominant CD8+ T cell clones present at baseline were expanded at 12 months post-transplant, suggesting these clones were not effectively eradicated during treatment. In contrast, the dominant CD4+ T cell clones present at baseline were undetectable at 12 months, and the reconstituted CD4+ T cell repertoire was predominantly composed of new clones.

The results also suggest the possibility that differences in repertoire diversity early in the reconstitution process might be associated with clinical outcomes. Nineteen patients who responded to treatment had a more diverse repertoire two months following transplant compared to four patients who did not respond. Despite the low number of non-responders, these comparisons approached statistical significance and point to the possibility that complexity in the T cell compartment may be important for establishing immune tolerance.

This is one of the first studies to quantitatively compare the baseline T cell repertoire with the reconstituted repertoire following autologous stem cell transplant, and provides a previously unseen in-depth analysis of how the immune system reconstitutes itself following immune-depleting therapy.

About The Immune Tolerance Network

The Immune Tolerance Network (ITN) is a research consortium sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The ITN develops and conducts clinical and mechanistic studies of immune tolerance therapies designed to prevent disease-causing immune responses, without compromising the natural protective properties of the immune system. Visit http://www.immunetolerance.org for more information.

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The above story is based on materials provided by Immune Tolerance Network. Note: Materials may be edited for content and length.

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Deep TCR sequencing reveals extensive renewal of the T cell repertoire following autologous stem cell transplant in MS

PUBLIC RELEASE DATE:

17-Feb-2014

Contact: Philip Bernstein, Ph.D. ITNCommunications@immunetolerance.org 240-235-6132 Immune Tolerance Network

WA, Seattle (February 17, 2014) A new study describes the complexity of the new T cell repertoire following immune-depleting therapy to treat multiple sclerosis, improving our understanding of immune tolerance and clinical outcomes.

In the Immune Tolerance Network's (ITN) HALT-MS study, 24 patients with relapsing, remitting multiple sclerosis received high-dose immunosuppression followed by a transplant of their own stem cells, called an autologous stem cell transplant, to potentially reprogram the immune system so that it stops attacking the brain and spinal cord. Data published today in the Journal of Clinical Investigation quantified and characterized T cell populations following this aggressive regimen to understand how the reconstituting immune system is related to patient outcomes.

ITN investigators used a high-throughput, deep-sequencing technology (Adaptive Biotechnologies, ImmunoSEQTM Platform) to analyze the T cell receptor (TCR) sequences in CD4+ and CD8+ cells to compare the repertoire at baseline pre-transplant, two months post-transplant and 12 months post-transplant.

Using this approach, alongside conventional flow cytometry, the investigators found that CD4+ and CD8+ lymphocytes exhibit different reconstitution patterns following transplantation. The scientists observed that the dominant CD8+ T cell clones present at baseline were expanded at 12 months post-transplant, suggesting these clones were not effectively eradicated during treatment. In contrast, the dominant CD4+ T cell clones present at baseline were undetectable at 12 months, and the reconstituted CD4+ T cell repertoire was predominantly comprised of new clones.

The results also suggest the possibility that differences in repertoire diversity early in the reconstitution process might be associated with clinical outcomes. Nineteen patients who responded to treatment had a more diverse repertoire two months following transplant compared to four patients who did not respond. Despite the low number of non-responders, these comparisons approached statistical significance and point to the possibility that complexity in the T cell compartment may be important for establishing immune tolerance.

This is one of the first studies to quantitatively compare the baseline T cell repertoire with the reconstituted repertoire following autologous stem cell transplant, and provides a previously unseen in-depth analysis of how the immune system reconstitutes itself following immune-depleting therapy.

###

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Extensive renewal of the T cell repertoire following autologous stem cell transplant in MS

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Newswise WA, Seattle (February 17, 2014) A new study describes the complexity of the new T cell repertoire following immune-depleting therapy to treat multiple sclerosis, improving our understanding of immune tolerance and clinical outcomes.

In the Immune Tolerance Networks (ITN) HALT-MS study, 24 patients with relapsing, remitting multiple sclerosis received high-dose immunosuppression followed by a transplant of their own stem cells, called an autologous stem cell transplant, to potentially reprogram the immune system so that it stops attacking the brain and spinal cord. Data published today in the Journal of Clinical Investigation (http://www.jci.org/articles/view/71691?key=b64763243f594bab6646) quantified and characterized T cell populations following this aggressive regimen to understand how the reconstituting immune system is related to patient outcomes.

ITN investigators used a high-throughput, deep-sequencing technology (Adaptive Biotechnologies, ImmunoSEQTM Platform) to analyze the T cell receptor (TCR) sequences in CD4+ and CD8+ cells to compare the repertoire at baseline pre-transplant, two months post-transplant and 12 months post-transplant.

Using this approach, alongside conventional flow cytometry, the investigators found that CD4+ and CD8+ lymphocytes exhibit different reconstitution patterns following transplantation. The scientists observed that the dominant CD8+ T cell clones present at baseline were expanded at 12 months post-transplant, suggesting these clones were not effectively eradicated during treatment. In contrast, the dominant CD4+ T cell clones present at baseline were undetectable at 12 months, and the reconstituted CD4+ T cell repertoire was predominantly comprised of new clones.

The results also suggest the possibility that differences in repertoire diversity early in the reconstitution process might be associated with clinical outcomes. Nineteen patients who responded to treatment had a more diverse repertoire two months following transplant compared to four patients who did not respond. Despite the low number of non-responders, these comparisons approached statistical significance and point to the possibility that complexity in the T cell compartment may be important for establishing immune tolerance.

This is one of the first studies to quantitatively compare the baseline T cell repertoire with the reconstituted repertoire following autologous stem cell transplant, and provides a previously unseen in-depth analysis of how the immune system reconstitutes itself following immune-depleting therapy.

About The Immune Tolerance Network The Immune Tolerance Network (ITN) is a research consortium sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The ITN develops and conducts clinical and mechanistic studies of immune tolerance therapies designed to prevent disease-causing immune responses, without compromising the natural protective properties of the immune system. Visit http://www.immunetolerance.org for more information.

###

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Deep TCR Sequencing Reveals Extensive Renewal of the T Cell Repertoire Following Autologous Stem Cell Transplant in ...

StemCells, Inc. Expands Phase I/II Spinal Cord Injury Trial to North America

NEWARK, Calif., Jan. 10, 2014 (GLOBE NEWSWIRE) -- StemCells, Inc. (Nasdaq:STEM) announced today that a team at the University of Calgary successfully transplanted its first subject in the Company's Phase I/II clinical trial in chronic spinal cord injury, with the Company's proprietary HuCNS-SC human neural stem cells. The ninth subject to enroll in the trial, which was initiated in Switzerland, is the first spinal cord injury patient to have undergone transplantation in North America. This expansion from a single-site, single-country study to a multi-site, multi-country program accelerates the current trial, which should complete enrollment of the remaining three patients this quarter, and pave the way for a controlled Phase II efficacy study that StemCells, Inc. plans to initiate mid-year to further investigate its HuCNS-SC product candidate as a treatment for spinal cord injury.

"With this transplantation in Canada, we have the first international trial investigating neural stem cells for spinal cord injury," said Stephen Huhn, M.D., FACS, FAAP, Vice President, CNS Clinical Research at StemCells, Inc. "The 12-month data from the first cohort has demonstrated a favorable safety profile, and sensory gains first detected in two of the three subjects at the six-month assessment have persisted. The third subject remains stable. We are extremely encouraged with the progress of our spinal cord injury program and the transition into an international study will accelerate completion of enrollment."

Steve Casha, M.D., Ph.D., FRCSC, the principal investigator at the University of Calgary, added, "We are proud to be the first center to enroll a subject in North America. This important research is yielding critical insight into the use of stem cells in treating spinal cord injury patients. The results should serve as a solid foundation for the Company's planned Phase II controlled efficacy study and represents an important step in the development of this promising technology."

"We have closely followed the conduct of the StemCells, Inc. trial at the University of Zurich, under the direction of Dr. Armin Curt," said Michael Fehlings M.D., Ph.D., FACS, FRCSC. Dr. Fehlings is Medical Director of the Krembil Neuroscience Centre, Professor of Neurosurgery at the University of Toronto, head of the Spinal Program at the Toronto Western Hospital, and principal investigator for the trial at the University of Toronto. "There is a large unmet medical need for treatments in spinal cord injury. The opening of sites in North America is great news for the worldwide community of patients and their families, as well as for researchers. There is a strong rationale to explore novel therapeutic approaches to treating spinal cord injury, and we are pleased to be working with StemCells at the forefront of this trailblazing study."

About the StemCells, Inc. Spinal Cord Injury Clinical Trial

The Company's Phase I/II clinical trial is designed to assess both safety and preliminary efficacy of HuCNS-SC cells as a treatment for chronic spinal cord injury. The Company plans to enroll 12 subjects with thoracic (chest-level) neurological injuries at the T2-T11 level, classified as complete or incomplete according to the American Spinal Injury Association Impairment Scale.

To date, nine patients have been enrolled and transplanted with HuCNS-SC cells.Each of the first three subjects suffered a complete injury prior to enrolling in the study. Twelve months after transplantation of the HuCNS-SC cells, data showed multi-segment gains in sensory function in two of the first three subjects, one of which converted from a complete injury classification to an incomplete injury.The third subject in this cohort remained stable, 12 months after transplantation. The company expects to report additional interim data on both the first and second cohorts by mid-2014.

The trial is currently enrolling spinal cord injury patients at three centers: the University of Calgary; the University of Toronto; and at Balgrist University Hospital, University of Zurich, a world-leading medical center for spinal cord injury and rehabilitation. Patients who may qualify and are interested in participating in the study in North America should contact the University of Calgary at 403-944-4334 or the University of Toronto at 416-603-5285. For information on enrollment in Switzerland, interested parties may contact the study nurse either by phone at +41 44 386 39 01, or by email at stemcells.pz@balgrist.ch.

All subjects who enroll in the trial will receive HuCNS-SC cells through direct transplantation into the spinal cord and will undergo temporary treatment with immunosuppressive drugs.Evaluations will be regularly performed in the post-transplant period in order to monitor and assess the safety of the HuCNS-SC cells, the surgery and the immunosuppression, as well as to measure any change in neurological function.Preliminary efficacy will be evaluated based on defined clinical endpoints, such as changes in sensation, motor function and bowel/bladder function.The Company intends to follow the effects of this intervention long term, and each of the subjects will be invited to enroll in a separate four-year observational study after completing the Phase I/II study.In addition, the Company plans to initiate a controlled Phase II efficacy trial in in spinal cord injury in 2014.

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StemCells, Inc. Expands Phase I/II Spinal Cord Injury ...

By Matt Richardson Photos by Ed Mulholland

Junior middleweight Boyd Melson has a fight scheduled for tomorrow night at the Roseland Ballroom in Manhattan against Donald Ward. Its a fight that Melson (13-1-1, 4 KOs) says he expects will be difficult, despite Ward being a late replacement for veteran Mike Ruiz. Its a fight, however, thats relatively small in relation to the one Melson fights on a daily basis.

Thats because Melson, an Army captain in the U.S. Army Reserves, is also battling a much tougher foe: spinal cord injuries. As a boxer who donates his full purses to spinal cord research, its easy to say he has a dog in this fight and its one where hes continuing to punch, despite the odds.

Were trying to bring awareness to spinal cord injuries and fund a clinical trial to happen here in the U.S, explained Melson. Theres a clinical trial thats going to be happening at the end of this year that a doctor named Dr. Wise Young is working on. Hes doing a trial here hopefully in New York and New Jersey, before this year is out, where hes going to be using umbilical cord cells and injecting them into the spinal cord. He already did this in China and hes using that data to get FDA approval here.

15 out of the 20 patients he did that were paralyzed after seven years, one of them was as long as 19 years paralyzed, Melson continued. But 15 out of the 20 are walking now with a walker and no human assistance. Its out of this world. Its a miracle. Its real frustrating for me to know that in another part of the world we may have a cure for this and its not here yet. It stinks.

Despite his being profiled in a series of publications and television programs, Melson said theres still a way to go in matching the awareness of the issue to a potential cure.

Its still a big fight, he admitted. Maybe, locally in New York people know about it. Or theyll just know that I donate my purses. A lot of them think its stem cell research, which is not correct. That happened because theyre taking stem cells from the umbilical cord for this study but theyre adult stem cells. They were donated after the baby was born. But there are plenty of different types of therapies people are using, going outside stem cells. This one just happens to be using it but its to cure paralysis, not to study stem cells.

Melson isnt alone in his aim to obtain more spinal cord injury research and has even secured the support of a series of other fighters, including Steve Cunningham, Demetrius Andrade, Deandre Latimore, Edgar Santana and Danny Jacobs on his Team Fight to Walk.

Those are some pretty strong names right there, he said.

Hes right.

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Melson keeps fighting

Up To 500,000 Spinal Cord Injuries Per Year Worldwide The World Health Organization says as many as 500,000 people suffer spinal cord injuries every year. And it says people with such injuries are much more likely to die early. Recently, the World Health Organization released a report called International Perspectives on Spinal Cord Injuries. Alana Officer works at the WHO. She says spinal cord injuries do more than just cause paralysis, or lack of movement. There are a lot more associated health problems, such as difficulty with bowel and bladder function, difficulty with sexual function, associated problems around mental health conditions. So its much broader than just experiencing paralysis. Alana Officer is the WHOs Coordinator for Disability and Rehabilitation. She says the main causes of spinal cord injuries are traffic accidents, falls and violence. She says some causes are more common in certain areas. For example, road traffic crashes are the main contributors of spinal cord injury in Africa and the Western Pacific region. Falls tend to be the leading cause in Southeast Asia and the Middle East. And then we have high rates of violence in certain countries. We have high rates in the U.S. We have high rates in South Africa. And then weve also got the non-traumatic causes of spinal cord injuries, such as tumors and cancers, tuberculosis and spinabifida. Most people think of tuberculosis as a lung disease. But in some African countries, it is responsible for about one third of the non-violent spinal cord injuries. The birth defect spinabifida causes damage to the spine. In severe cases, it can affect walking and daily activities. Health officials say they do not yet know the exact cause of spinabifida. But they say it may be linked to genes and the environment. Alana Officer says more men than women suffer spinal cord injuries. Theres a ratio of about two-to-one of males to females. Men tend to be more likely to experience spinal cord injury between the ages of about 20 and 29 -- women, or certainly girls much younger, between sort of 15 and 19. So thats our first peak in young people. And then we get a second peak, interestingly, in older people. And the major driver of that is falls, tumors, cancer, et cetera. She says the main reason people with spinal cord injuries are more likely to die early is lack of medical care. A lot of people with spinal cord injuries, certainly in low- and middle- income countries, do not get appropriate emergency response care. Mortality rates are very strongly affected by the quality of the health care system. For example, if youre in a low-income country, you are three times more likely of dying in (a) hospital following a spinal cord injury than you would be in a high-income country. Ms. Officer says many of the causes of spinal cord injury deaths in poor countries are preventable. These include urinary tract infections and pressure sores, also known as bedsores. These are areas of damaged skin caused by a person staying in one position too long. Bedsores are usually not life-threatening problems in wealthy countries. People with spinal cord injuries can live pretty much the same amount of time as somebody without a spinal cord injury. Theres a slight difference, but certainly life expectancy has increased considerably in high-income countries. And its not the case in low- income countries. Experts suggest immediate action if a spinal cord injury is suspected, including immobilization of the spine, restricting its movement. The WHO says that should be followed by what it calls, care appropriate to the level and severity of the injury, degree of instability of the spine and compression of nerves. It also suggests skilled rehabilitation and mental health services. The WHO notes that up to 30 percent of people with spinal cord injuries show clinically-significant signs of depression. There is currently no cure for paralysis from spinal cord injuries, but many researchers are looking for one. Alana Officer says there is much that can be done to prevent such injuries -- including building safer roads and vehicles, reducing drinking and driving and wearing seatbelts. Other measures include improving safety in sports and the workplace, and adding window guards to windows. She says spinal cord injuries would be reduced if doctors could identify and treat tuberculosis earlier and by improving nutrition to reduce spinabifida cases. Scientists Create Lung Tissue from Stem Cells Finally, scientists have used stem cell technology to create working lung cells. Researchers say stem cells also could be used to create new drugs to treat diseases that restrict breathing. And they think the cells could one day create tissue for lung transplant operations. The research is another step toward what is being called personalized medicine. Over the past several years, scientists have used stem cells and growth factors to force the bodys master cells to create other cells. This process has created heart, intestinal, liver, nerve and insulin-producing cells as possible replacements for diseased organs.

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Newswise NEW YORK, NY (February 6, 2014) In most cases of amyotrophic lateral sclerosis (ALS), or Lou Gehrigs disease, a toxin released by cells that normally nurture neurons in the brain and spinal cord can trigger loss of the nerve cells affected in the disease, Columbia researchers reported today in the online edition of the journal Neuron.

The toxin is produced by star-shaped cells called astrocytes and kills nearby motor neurons. In ALS, the death of motor neurons causes a loss of control over muscles required for movement, breathing, and swallowing. Paralysis and death usually occur within 3 years of the appearance of first symptoms.

The report follows the researchers previous study, which found similar results in mice with a rare, genetic form of the disease, as well as in a separate study from another group that used astrocytes derived from patient neural progenitor cells. The current study shows that the toxins are also present in astrocytes taken directly from ALS patients.

I think this is probably the best evidence we can get that what we see in mouse models of the disease is also happening in human patients, said the studys senior author, Serge Przedborski, MD, PhD, the Page and William Black Professor of Neurology (in Pathology and Cell Biology), Vice Chair for Research in the Department of Neurology, and co-director of Columbias Motor Neuron Center.

The findings also are significant because they apply to the most common form of ALS, which affects about 90 percent of patients. Scientists do not know why ALS develops in these patients; the other 10 percent of patients carry one of 27 genes known to cause the disease.

Now that we know that the toxin is common to most patients, it gives us an impetus to track down this factor and learn how it kills the motor neurons, Dr. Przedborski said. Its identification has the potential to reveal new ways to slow down or stop the destruction of the motor neurons.

In the study, Dr. Przedborski and study co-authors Diane Re, PhD, and Virginia Le Verche, PhD, associate research scientists, removed astrocytes from the brain and spinal cords of six ALS patients shortly after death and placed the cells in petri dishes next to healthy motor neurons. Because motor neurons cannot be removed from human subjects, they had been generated from human embryonic stem cells in the Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, also at CUMC.

Within two weeks, many of the motor neurons had shrunk and their cell membranes had disintegrated; about half of the motor neurons in the dish had died. Astrocytes removed from people who died from causes other than ALS had no effect on the motor neurons. Nor did other types of cells taken from ALS patients.

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Toxin from Brain Cells Triggers Neuron Loss in Human ALS Model

New details about how motor neurons die in ALS have been uncovered by a new cell-culture system that combines spinal cord or brain cells from ALS patients with human motor neurons. The culture system shows that patient astrocytes (shown here with a blue-stained nucleus) release a toxin that kills motor neurons via a recently discovered process described as a controlled cellular explosion. Image: Diane Re.

NEW YORK, NY (February 6, 2014) In most cases of amyotrophic lateral sclerosis (ALS), or Lou Gehrigs disease, a toxin released by cells that normally nurture neurons in the brain and spinal cord can trigger loss of the nerve cells affected in the disease, Columbia researchers reported today in the online edition of the journal Neuron.

The toxin is produced by star-shaped cells called astrocytes and kills nearby motor neurons. In ALS, the death of motor neurons causes a loss of control over muscles required for movement, breathing, and swallowing. Paralysis and death usually occur within 3 years of the appearance of first symptoms.

The report follows the researchers previous study, which found similar results in mice with a rare, genetic form of the disease, as well as in a separate study from another group that used astrocytes derived from patient neural progenitor cells. The current study shows that the toxins are also present in astrocytes taken directly from ALS patients.

I think this is probably the best evidence we can get that what we see in mouse models of the disease is also happening in human patients, said the studys senior author, Serge Przedborski, MD, PhD, the Page and William Black Professor of Neurology (in Pathology and Cell Biology), Vice Chair for Research in the department of Neurology, and co-director of Columbias Motor Neuron Center.

The findings also are significant because they apply to the most common form of ALS, which affects about 90 percent of patients. Scientists do not know why ALS develops in these patients; the other 10 percent of patients carry one of 27 genes known to cause the disease.

Now that we know that the toxin is common to most patients, it gives us an impetus to track down this factor and learn how it kills the motor neurons, Dr. Przedborski said. Its identification has the potential to reveal new ways to slow down or stop the destruction of the motor neurons.

In the study, Dr. Przedborski and study co-authors Diane Re, PhD, and Virginia Le Verche, PhD, associate research scientists, removed astrocytes from the brain and spinal cords of six ALS patients shortly after death and placed the cells in petri dishes next to healthy motor neurons. Because motor neurons cannot be removed from human subjects, they had been generated from human embryonic stem cells in the Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, also at CUMC.

Within two weeks, many of the motor neurons had shrunk and their cell membranes had disintegrated; about half of the motor neurons in the dish had died. Astrocytes removed from people who died from causes other than ALS had no effect on the motor neurons. Nor did other types of cells taken from ALS patients.

Astrocytes from ALS patients release a toxin that kills human motor neurons. Left: a disintegrating motor neuron on top of human astrocytes (blue). Right: a healthy motor neuron on top of astrocytes from people unaffected by ALS. Image: Diane Re.

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Medical Center Researchers Create Human ALS Model That May Lead to New Therapies

A new method of producing stem cells is being described as a "game-changing" scientific breakthrough.

It is said that the research, carried out by scientists in Japan, could hail a new era of personalised medicine, offering hope to sufferers of diseases such as stroke, heart disease and spinal cord injuries.

The scientists bathed blood cells in a weak acidic solution for half an hour, which made the adult cells shrink and go back to their embryonic stem cell state. Using this process, a patient's own specially created stem cells could then be re-injected back into the body to help mend damaged organs.

The scientists in Japan used mice in this experiment but believe the approach may also work on human cells too.

The new method - much cheaper and faster than before - is being heralded as revolutionary, and could bring stem cell therapy a step closer, and all without the controversy linked to the use of human embryos.

But there is still research that some find ethically questionable.

On Inside Story: Is the controversy over using human embryos over? And how should ethics determine medical progress?

Presenter: Shiulie Ghosh

Guests:

Dusko Ilic, a reader in Stem Cell Science at King's College London School ofMedicine

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The ethics of medical progress

PUBLIC RELEASE DATE:

30-Jan-2014

Contact: Tom Vasich tmvasich@uci.edu 949-824-6455 University of California - Irvine

Irvine, Calif., Jan. 30, 2014 Two UC Irvine research teams will receive $1.54 million to further studies on the fundamental structure and function of stem cells. Their work will aid efforts to treat and cure a range of ailments, from cancer to neurological diseases and injuries.

The California Institute for Regenerative Medicine awarded the two grants today to Lisa Flanagan and Peter Donovan of the Sue & Bill Gross Stem Cell Research Center as part of its basic biology awards program.

CIRM's governing board gave 27 such grants worth $27 million to 11 institutions statewide. The funded projects are considered critical to the institute's mission of investigating the underlying mechanisms of stem cell biology, cellular plasticity and cellular differentiation in order to create a foundation for future translational and clinical advances.

Today's grants bring total CIRM funding at UC Irvine to $98.8 million.

"Innovative basic research like this paves the way to better designs for the use of stem cells," said Sidney Golub, director of the Sue & Bill Gross Stem Cell Research Center. "Even more importantly, it can open up entirely new approaches based on a better understanding of how stem cells function."

In one project, Flanagan and her UC Irvine colleagues will utilize a $1 million grant to study what happens on the surface of early-stage neural stem cells that causes them to develop into either neurons or astrocytes different kinds of brain and spinal cord cells. In the course of this work, the team aims to uncover specific properties of human stem cells used to treat neurological diseases and injuries.

"We expect this knowledge will enhance the benefit of these cells in transplants by enabling more control over what sort of mature cells will be formed from transplanted cells," said Flanagan, an assistant professor of neurology, biomedical engineering and anatomy & neurobiology. "We hope our research will greatly improve the identification, isolation and utility of certain types of human neural stem cells."

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UC Irvine stem cell researchers awarded $1.54 million in state funding

Professor Austin Smith of Cambridge University, writing in the Journal Nature said the new cells could be seen as a blank slate from which any cell could emerge depending on its environment.

Remarkably, instead of triggering cell death or tumour growth as might be expected, a new cell state emerges that exhibits and unprecedented potential for differentiation into every possible cell type, he said.

The discovery has been hailed as incredible by scientists who believe it will speed up the advancement of personalised medicine.

Stem cells offer the possibility of a renewable source of replacement cells and tissues to treat diseases including Alzheimer's, spinal cord injury, stroke, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis.

They could be used to regenerate organs, stimulate the growth of new blood vessels, or create skin grafts.

(This) approach in the mouse is the most simple, lowest cost and quickest method to generate pluripotent cells from mature cells, said Professor Chris Mason, Chair of Regenerative Medicine Bioprocessing, at University College London.

If it works in man, this could be the game changer that ultimately makes a wide range of cell therapies available using the patients own cells as starting material the age of personalised medicine would have finally arrived.

Who would have thought that to reprogram adult cells to an embryonic stem cell-like (pluripotent) state just required a small amount of acid for less than half an hour an incredible discovery.

Professor Mason said the development was likely to speed up the development of technology in everyday clinical practice although warned that was still years away.

Dr Dusko Ilic, Reader in Stem Cell Science, Kings College London, said the findings were revolutionary.

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'Stem cells' created in less than 30 minutes in 'groundbreaking' discovery

CALGARY- A Winnipeg paramedic has become the first Canadian to take part in an international clinical trial involving the treatment of spinal cord injuries using stem cells.

Alex Petric was injured last year during a winter vacation in Panama.

I misjudged the water and just dove in, the 29-year-old recalls. I hit shallow water and became paralyzed immediately.

Petric, now a paraplegic, became involved with the trial just four months after his injury.

Its a phase one trial which means that its looking at the safety and tolerability of the procedure, explains Dr. Steve Casha, medical team lead for the University of Calgary.

A Swiss company, calledStem Cells Incorporatedis the driving force behind the research. A team in Switzerland has already treated eight other spinal cord patients.

During the trial, researchers must first identify the precise location of Petrics spinal cord injury. Then, stem cells are injected into two sites above and two sites below the injury to hopefully recreate lost tissue.

What these cells will hopefully do, and what they seem to do from previous clinical studies is take up residence in the spinal cord. They are a self-renewing population and they can differentiate or become various cells, Dr. Casha explains.

While the first phase of the trial focuses on safety, the ultimate goal is to develop a cure for spinal cord injuries. So far, two patients in the study have regained sensation.

Petric says his expectations are realistic, but his dream is to walk again.

Originally posted here:
New trial offers new hope for those with spinal cord injuries