Funding of $67.5M will come from Genome Canada ($40 million), CIHR ($22.5 million) and the Cancer Stem Cell Consortium ($5 million). Projects will be funded for a maximum of four years. To qualify for funding, researchers must obtain matching funding that at is least equal to that provided through the competition, which will bring the total investment in this research area to close to $140 million. Matching funding is typically derived from provincial, academic, private sector or international sources.

Details about the competition are available here.

Press releases, dated January 31, 2012, about the federal government’s support for personalized medicine, are available here and here.

Source:
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Source:
http://intlstemcell.blogspot.com/feeds/posts/default?alt=rss

The Center for Genetics and Society has filed a brief statement with the Institute of Medicine panel examining the performance of the California stem cell agency, expressing the hope that the inquiry will include “a broader range of sources.”

Marcy Darnovsky, associate executive director of the Berkeley group, said that “a meaningful review by (the IOM) committee could make an important contribution to needed changes at the agency.” Darnovsky’s organization has followed the stem cell effort since its inception.

She noted that CIRM is “a public agency spending increasingly scarce public resources” and has raised the possibility of seeking another multibillion dollar bond measure from voters.

The IOM inquiry has finished half of its public process and is yet to hear an independent analysis of the stem cell agency, which is paying $700,000 for the study.

Earlier Darnovsky told the California Stem Cell Report that the Institute of Medicine has not contacted her organization for comments, although she has spoken with the public relations person for the IOM.

Here is the text of Darnovsky’s statement sent to the IOM.

“The Center for Genetics and Society is a public interest organization working to ensure responsible uses and effective societal governance of human genetic and reproductive technologies.  We support embryonic stem cell research, but have been concerned for some years about a number of aspects of the field, and of the California Institute of Regenerative Medicine in particular.

“We have been closely following CIRM since the campaign for Proposition 71 that established it in 2004. We have attended numerous meetings of the agency’s governing board and Standards Working Group, worked with other public interest groups who share our concerns about CIRM, written frequently about CIRM in our publications, and been cited dozens of times in articles about CIRM in key state and national news outlets.

“In 2006, we published The California Stem Cell Program at One Year: A Progress Report, which assessed CIRM’s performance to that date and offered recommendations. See http://www.geneticsandsociety.org/downloads/200601report.pdf

“In 2008, CGS policy analyst Jesse Reynolds gave invited testimony to the Little Hoover Commission’s hearing on CIRM. See http://www.geneticsandsociety.org/article.php?id=4386

“We are encouraged that the Institute of Medicine is undertaking an independent assessment of CIRM, though we hope that you will invite input from a broader range of sources than were represented at the meeting last month in San Francisco. With key questions about the future of CIRM unresolved, and its leadership contemplating a campaign for another bond measure.

“As I wrote in a recent commentary that expressed our disappointment with the roster of speakers at last month’s hearing,

“Ballot measure or no ballot measure, CIRM will continue to disperse the public money it controls – another billion and a half dollars. This is a public agency spending increasingly scarce public resources. It is funding a field of research in which we place great hopes for medical and scientific advances. These factors make it all the more crucial that CIRM follow the basics of good governance and public accountability, and eschew the hyperbole and exaggerated promises that have tainted stem cell research for so long.

“See  http://www.geneticsandsociety.org/article.php?id=6045

“Please let us know if we can be of help. We would be very glad to share our insights and recommendations.”

Source:
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Here is the text of questions from the California Stem Cell Report and answers from the Institute of Medicine concerning its plans to secure independent perspectives during the IOM’s examination of the California stem cell agency. So far, the IOM has not heard publicly from any independent sources.

Christine Stencel, a spokeswoman for the IOM, responded for the IOM. She first gave an overall statement. Then she answered the specific queries. We have inserted the questions from the California Stem Cell Report into her text  in order to make the Q&A easier to follow.

The IOM’s general comment:

“The committee and staff are planning their next info gathering sessions. Specifics of these events haven’t all been worked out yet, but one overall point is that the committee believes it is important to hear the full range of perspectives and experiences with CIRM and the committee members are actively pursuing sources of information that will allow them to adequately answer the questions they’ve been tasked to explore. The study is ongoing and there are still a lot of people and resources to tap and information to learn.

“To your specific questions:”

California Stem Cell Report:

“Does the IOM have plans to talk with or seek statements from such groups as the Little Hoover Commission and the Center for Genetics and Society or state Controller John Chiang?”

IOM response:

“Yes. And the committee is reading all the past reviews of CIRM.”

California Stem Cell Report:

“Does the IOM plan to seek comments from grant applicants rejected by CIRM, particularly businesses? If so how many? How would such applicants be selected by the IOM for interviews or comments?”

IOM response:

“Yes, the committee wishes to hear these perspectives and is seeking ways to get them.”

California Stem Cell Report:

“Does the IOM plan to do more than passively post forms for comment from others? Does it plan to email those forms, for example, to all CIRM grant recipients and applicants who were rejected? Does it plan to follow up to be sure an adequate response is generated?”

IOM response:

“The IOM is proactively working to get survey responses and encouraging people to respond.”

California Stem Cell Report:

“What does the IOM mean by ‘industry partners’ on its (online) forms for comment?”

IOM response:

“Industry partners means CIRM investigators representing for-profit companies.”

California Stem Cell Report:

“Does the IOM plan to examine both public and private complaints about conflicts of interest on the part of CIRM grant reviewers? By private, I mean written complaints to CIRM that the agency retains but has not made public.”

IOM response:

“The committee is looking into the grants review process and working to make sure that the members obtain all relevant insights and information. The committee members intend to invite people who can provide a broad range of experiences with and perspectives of CIRM to the upcoming meeting in April.”

The California Stem Cell Report later asked the IOM if it wanted to comment on a quote that we were considering using, which said,

“In the eyes of the IOM, scientists who draw funding from CIRM and other sources are ‘independent.’ They look at these things differently than regular people would.”

The IOM responded,

“As to the quote you sent, as a response we would just reiterate that the committee is methodically going about its task and during the course of the study aims to gather the full range of information, experiences, and insights relevant to CIRM from a full range of sources.”

Source:
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The blue-ribbon panel examining the performance of the $3 billion California stem cell agency is midway through its public process and is yet to hear from a single independent witness during its open sessions.

The panel’s report and recommendations are due this fall and are expected to have a major impact on the seven-year-old agency and its future.

So far, the IOM panel has heard only from employees or directors of the agency and persons representing institutions that have received $418 million in CIRM cash.

The panel of scientists and academics was put together by the prestigious Institute of Medicine under a $700,000 contract with the stem cell agency itself. At the 2010 meeting during which agency directors approved the contract, they expressed hope that the IOM panel’s findings would bolster public support for another multibillion dollar bond measure for the agency, which expects to run out of funds for new grants in 2017.

Last week, the California Stem Cell Report asked the IOM about its plans to gather independent or critical information about the stem cell agency’s performance. With only one more California public meeting scheduled, the IOM said that it is seeking the “full range of perspectives” but did not respond directly to questions about the specifics of how it is going to fulfill that task.

None of the four organizations in California that have an independent perspective on CIRM have been contacted by the IOM, the California Stem Cell Report has been told. They are the state’s Little Hoover Commission, the Center for Genetics and Society, Consumer Watchdog and the Citizens Financial Accountability and Oversight Committee, which is the only state body specifically charged with oversight of CIRM and its directors and which is chaired by the state’s top fiscal officer, Controller John Chiang. A spokeswoman for the IOM panel said, however, it plans to touch base with at least some of the four.

In response to questions from the California Stem Cell Report, Christine Stencel, the IOM spokeswoman, said the IOM also wants to hear comments from businesses whose applications have been rejected by CIRM. However, she said the panel is still working on “ways to get them.” She did not respond directly to questions about how many of such businesses would be interviewed or how they would be selected. The tiny number of CIRM grants to business is a sore spot with industry. Even directors and CIRM’s own “external review” panel have said much more is needed.

In response to a question about complaints about conflicts of interest on the part of CIRM reviewers, Stencel was also non-specific, saying only that the panel wants to “obtain all relevant insights.” She did not respond directly to a question about whether the panel would examine “private complaints” filed with CIRM by rejected applicants.

Currently the IOM has forms posted online that interested parties, if they know about the existence of the forms, can use to comment on CIRM. We asked whether the panel plans to do more than passively post the forms, specifically whether it plans to email them to all CIRM applicants who were rejected. We also asked about IOM plans to follow up to generate an adequate response. Stencel said the IOM is “proactively working” to get survey responses but did not say what specific steps it was taking.

Our comment?

The IOM has a well-deserved reputation for rigor and thoroughness. However, the IOM is all but unknown to 99 pecent of the public, which will be the ultimate consumer of its findings on the stem cell agency. The fact that the IOM is being paid $700,000 by CIRM will undoubtedly raise questions in the minds of some about IOM’s own objectivity. The panel itself consists of persons who have like-minded interests and sympathy with CIRM and its 485 grant recipients. No member of the panel is likely to publicly discourage more scientific research, even if CIRM is deemed to be failing to fulfill the voters expectations in 2004 when they created the agency. All the more reason to aggressively seek out those with contrary views about CIRM’s performances, if the IOM’s report is to have maximum credibility.

Earlier this week we heard from a knowledgeable and longtime observer of the research scene, who said that the IOM looks at things “differently than regular people” and views scientists who receive funding from CIRM as “independent.” The IOM’s Stencel responded by reiterating that the IOM is seeking the full range of information from the full range of sources.

The IOM evaluation of CIRM’s performance is much too far along not to have progressed further with its attempts to hear from independent and critical voices about CIRM. Generalizations to the effect that “we are going to get to it” do not serve the panel well. The IOM should lay out publicly and quite specifically its plans to aggressively seek thoughtful analysis from parties that do not have financial or professional links to CIRM, as well as from those who feel they have received a short shrift from the $3 billion enterprise.

You can read the full text of the questions from the California Stem Cell Report and the IOM responses here.

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

The prestigious journal Nature today said that asking California voters for more billions for stem cell research in a few years “may strike residents as a luxury that they can ill afford.”

The comment came in a piece by Erika Check Hayden dealing with the future of the California stem cell agency, which is expected to run out of money for new grants in about 2017. She wrote,

“Given that California is facing severe budget shortfalls, several billion dollars more for stem-cell science may strike residents as a luxury that they can ill afford. It may also prove difficult for CIRM’s supporters to point to any treatments that have emerged from the state’s investment. So far, the agency has funded only one clinical trial using embryonic stem cells, and that was halted by its sponsor, Geron of Menlo Park, California, last November.

“Yet the institute has spent just over $1 billion on new buildings and labs, basic research, training and translational research, often for projects that scientists say are crucial and would be difficult to get funded any other way. So the prospect of a future without CIRM is provoking unease. ‘It would be a very different landscape if CIRM were not around,’ says Howard Chang, a dermatologist and genome scientist at Stanford University in California.”

Chang was a scheduled witness recently at a public meeting in California of the blue-ribbon Institute of Medicine panel examining the performance of the Golden State’s $3 billion stem cell research effort. Chang is the recipient of $3.2 million in CIRM funding. Hayden wrote,

“Chang has a CIRM grant to examine epigenetics in human embryonic stem cells, and is part of another CIRM-funded team that is preparing a developmental regulatory protein for use as a regenerative therapy. Both projects would be difficult to continue without the agency, he says. Federal funding for research using human embryonic stem cells remains controversial, and could dry up altogether after the next presidential election (see Nature 481, 421–423; 2012). And neither of Chang’s other funders — the US National Institutes of Health (NIH) and the Howard Hughes Medical Institute in Chevy Chase, Maryland — supports his interdisciplinary translational work. Irina Conboy, a stem-cell engineer at the University of California, Berkeley, who draws half of her lab’s funding from CIRM, agrees that in supporting work that has specific clinical goals, the agency occupies a niche that will not easily be filled by basic-research funders. ‘The NIH might say that the work does not have a strong theoretical component, so you’re not learning anything new,’ she says.”

Conboy was also a scheduled witness at the IOM hearing. She holds $2.2 million in CIRM grants.

Source:
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stem cell therapy mexico, Successfully Results – Video

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Athersys touts results of phase 1 blood diseases trial

NEW YORK & PETACH TIKVAH, Israel–(BUSINESS WIRE)– BrainStorm Cell Therapeutics Inc. (OTCBB: BCLI.OB – News), a leading developer of adult stem cell technologies and therapeutics, announced today that the prestigious Experimental Neurology Journal, published an article indicating that preclinical studies using cells that underwent treatment with Brainstorm’s NurOwn™ technology show promise in an animal model of Huntington’s disease. The article was published by leading scientists including Professor Melamed and Professor Offen of the Tel Aviv University.

In these studies, bone marrow derived mesenchymal stem cells secreting neurotrophic factors (MSC-NTF), from patients with Huntington’s disease, were transplanted into the animal model of this disease and showed therapeutic improvement.

“The findings from this study demonstrate that stem cells derived from patients with a neurodegenerative disease, which are processed using BrainStorm’s NurOwn™ technology, may alleviate neurotoxic signs, in a similar way to cells derived from healthy donors. This is an important development for the company, as it confirms that autologous transplantation may be beneficial for such additional therapeutic indications,” said Dr. Adrian Harel, BrainStorm’s CEO.

“These findings provide support once again that BrainStorm’s MSC-NTF secreting cells have the potential to become a platform that in the future will provide treatment for various neuro-degenerative diseases,” says Chaim Lebovits, President of BrainStorm. “This study follows previously published pre-clinical studies that demonstrated improvement in animal models of neurodegenerative diseases such as Parkinson’s, Multiple Sclerosis (MS) and neural damage such as optic nerve transection and sciatic nerve injury. Therefore, BrainStorm will consider focusing on a new indication in the near future, in addition to the ongoing Clinical Trials in ALS.”

BrainStrom is currently conducting a Phase I/II Human Clinical Trial for Amyotrophic Lateral Sclerosis (ALS) also known as Lou Gehrig’s disease at the Hadassah Medical center. Initial results from the clinical trial (which is designed mainly to test the safety of the treatment), that were announced last week, have shown that the Brainstorm’s NurOwn™ therapy is safe and does not show any significant treatment-related adverse events and have also shown certain signs of beneficial clinical effects.

To read the Article entitled ‘Mesenchymal stem cells induced to secrete neurotrophic factors attenuate quinolinic acid toxicity: A potential therapy for Huntington's disease’ by Sadan et al. please go to:

http://www.sciencedirect.com/science/article/pii/S0014488612000295

About BrainStorm Cell Therapeutics, Inc.

BrainStorm Cell Therapeutics Inc. is a biotech company developing adult stem cell therapeutic products, derived from autologous (self) bone marrow cells, for the treatment of neurodegenerative diseases. The company, through its wholly owned subsidiary Brainstorm Cell Therapeutics Ltd., 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 technology is currently in a Phase I/II clinical trials for ALS in Israel.

Safe Harbor Statement

Statements in this announcement other than historical data and information constitute “forward-looking statements” and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements, including, inter alia, regarding safety and efficacy in its human clinical trials and thereafter; the Company's ability to progress any product candidates in pre-clinical or clinical trials; the scope, rate and progress of its pre-clinical trials and other research and development activities; the scope, rate and progress of clinical trials we commence; clinical trial results; safety and efficacy of the product even if the data from pre-clinical or clinical trials is positive; uncertainties relating to clinical trials; risks relating to the commercialization, if any, of our proposed product candidates; dependence on the efforts of third parties; failure by us to secure and maintain relationships with collaborators; dependence on intellectual property; competition for clinical resources and patient enrollment from drug candidates in development by other companies with greater resources and visibility, and risks that we may lack the financial resources and access to capital to fund our operations. The potential risks and uncertainties include risks associated with BrainStorm's limited operating history, history of losses; minimal working capital, dependence on its license to Ramot's technology; ability to adequately protect its technology; dependence on key executives and on its scientific consultants; ability to obtain required regulatory approvals; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at http://www.sec.gov. The Company does not undertake any obligation to update forward-looking statements made by us.

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Stem Cell Therapy Shows Promise for Stroke, Studies Say

By Maureen Salamon
HealthDay Reporter

WEDNESDAY, Feb. 1 (HealthDay News) — Treating stroke patients with stem cells taken from their own bone marrow appears to safely help them regain some of their lost abilities, two small new studies suggest.

Indian researchers observed mixed results in the extent of stroke patients' improvements, with one study showing marked gains in daily activities, such as feeding, dressing and movement, and the other study noting these improvements to be statistically insignificant. But patients seemed to safely tolerate the treatments in both experiments with no ill effects, study authors said.

“The results are encouraging to know but we need a larger, randomized study for more definitive conclusions,” said Dr. Rohit Bhatia, a professor of neurology at the All India Institute of Medical Sciences in New Delhi, and author of one of the studies. “Many questions — like timing of transplantation, type of cells, mode of transplantation, dosage [and] long-term safety — need answers before it can be taken from bench to bedside.”

The studies are scheduled to be presented Wednesday and Thursday at the American Stroke Association's annual meeting in New Orleans.

Stem cells — unspecialized cells from bone marrow, umbilical cord blood or human embryos that can change into cells with specific functions — have been explored as potential therapies for a host of diseases and conditions, including cancer and strokes.

In one of the current studies, 120 moderately affected stroke patients ranging from 18 to 75 years old were split into two groups, with half infused intravenously with stem cells harvested from their hip bones and half serving as controls. About 73 percent of the stem cell group achieved “assisted independence” after six months, compared with 61 percent of the control group, but the difference wasn't considered statistically significant.

In the other study, presented by Bhatia, 40 patients whose stroke occurred between three and 12 months prior were also split into two groups, with half receiving stem cells, which were dissolved in saline and infused over several hours. When compared to controls, stroke patients receiving stem cell therapy showed statistically significant improvements in feeding, dressing and mobility, according to the study. On functional MRI scans, the stem cell recipients also demonstrated an increase in brain activity in regions that control movement planning and motor function.

Neither study yielded adverse effects on patients, which could include tumor development.

But Dr. Matthew Fink, chief of the division of stroke and critical care neurology at New York-Presbyterian Hospital/Weill Cornell Medical Center, said that the therapy's safety is the only thing the two studies seemed to demonstrate.

“The thing to keep in mind is that these are really phase one trials,” said Fink, also a professor of neurology at Weill Cornell Medical College. “I'm concerned that people get the idea that now stem cell treatment is available for stroke, and that's not the case.”

Fink noted that the cells taken from study participants' hip bones can only be characterized as “bone marrow aspirates” since the authors didn't prove that actual stem cells were extracted.

“They haven't really analyzed if they're stem cells and what they turn into when they go into circulation,” he added. “The best way to look at this is, it's very preliminary . . . when patients come to me to talk about it, I'm going to tell them it's years away before we know if this is going to work.”

Studies presented at scientific conferences should be considered preliminary until published in a peer-reviewed medical journal.

More information

The U.S. National Institutes of Health has more information on stem cells.

Copyright © 2012 HealthDay. All rights reserved.

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Stem cell therapy shows promise for stroke

ScienceDaily (Jan. 30, 2012) — Mouse skin cells can be converted directly into cells that become the three main parts of the nervous system, according to researchers at the Stanford University School of Medicine. The finding is an extension of a previous study by the same group showing that mouse and human skin cells can be directly converted into functional neurons.

The multiple successes of the direct conversion method could refute the idea that pluripotency (a term that describes the ability of stem cells to become nearly any cell in the body) is necessary for a cell to transform from one cell type to another. Together, the results raise the possibility that embryonic stem cell research and another technique called “induced pluripotency” could be supplanted by a more direct way of generating specific types of cells for therapy or research.

This new study, published online Jan. 30 in the Proceedings of the National Academy of Sciences, is a substantial advance over the previous paper in that it transforms the skin cells into neural precursor cells, as opposed to neurons. While neural precursor cells can differentiate into neurons, they can also become the two other main cell types in the nervous system: astrocytes and oligodendrocytes. In addition to their greater versatility, the newly derived neural precursor cells offer another advantage over neurons because they can be cultivated to large numbers in the laboratory — a feature critical for their long-term usefulness in transplantation or drug screening.

In the study, the switch from skin to neural precursor cells occurred with high efficiency over a period of about three weeks after the addition of just three transcription factors. (In the previous study, a different combination of three transcription factors was used to generate mature neurons.) The finding implies that it may one day be possible to generate a variety of neural-system cells for transplantation that would perfectly match a human patient.

“We are thrilled about the prospects for potential medical use of these cells,” said Marius Wernig, MD, assistant professor of pathology and a member of Stanford's Institute for Stem Cell Biology and Regenerative Medicine. “We've shown the cells can integrate into a mouse brain and produce a missing protein important for the conduction of electrical signal by the neurons. This is important because the mouse model we used mimics that of a human genetic brain disease. However, more work needs to be done to generate similar cells from human skin cells and assess their safety and efficacy.”

Wernig is the senior author of the research. Graduate student Ernesto Lujan is the first author.

While much research has been devoted to harnessing the pluripotency of embryonic stem cells, taking those cells from an embryo and then implanting them in a patient could prove difficult because they would not match genetically. An alternative technique involves a concept called induced pluripotency, first described in 2006. In this approach, transcription factors are added to specialized cells like those found in skin to first drive them back along the developmental timeline to an undifferentiated stem-cell-like state. These “iPS cells” are then grown under a variety of conditions to induce them to re-specialize into many different cell types.

Scientists had thought that it was necessary for a cell to first enter an induced pluripotent state or for researchers to start with an embryonic stem cell, which is pluripotent by nature, before it could go on to become a new cell type. However, research from Wernig's laboratory in early 2010 showed that it was possible to directly convert one “adult” cell type to another with the application of specialized transcription factors, a process known as transdifferentiation.

Wernig and his colleagues first converted skin cells from an adult mouse to functional neurons (which they termed induced neuronal, or iN, cells), and then replicated the feat with human cells. In 2011 they showed that they could also directly convert liver cells into iN cells.

“Dr. Wernig's demonstration that fibroblasts can be converted into functional nerve cells opens the door to consider new ways to regenerate damaged neurons using cells surrounding the area of injury,” said pediatric cardiologist Deepak Srivastava, MD, who was not involved in these studies. “It also suggests that we may be able to transdifferentiate cells into other cell types.” Srivastava is the director of cardiovascular research at the Gladstone Institutes at the University of California-San Francisco. In 2010, Srivastava transdifferentiated mouse heart fibroblasts into beating heart muscle cells.

“Direct conversion has a number of advantages,” said Lujan. “It occurs with relatively high efficiency and it generates a fairly homogenous population of cells. In contrast, cells derived from iPS cells must be carefully screened to eliminate any remaining pluripotent cells or cells that can differentiate into different lineages.” Pluripotent cells can cause cancers when transplanted into animals or humans.

The lab's previous success converting skin cells into neurons spurred Wernig and Lujan to see if they could also generate the more-versatile neural precursor cells, or NPCs. To do so, they infected embryonic mouse skin cells — a commonly used laboratory cell line — with a virus encoding 11 transcription factors known to be expressed at high levels in NPCs. A little more than three weeks later, they saw that about 10 percent of the cells had begun to look and act like NPCs.

Repeated experiments allowed them to winnow the original panel of 11 transcription factors to just three: Brn2, Sox2 and FoxG1. (In contrast, the conversion of skin cells directly to functional neurons requires the transcription factors Brn2, Ascl1 and Myt1l.) Skin cells expressing these three transcription factors became neural precursor cells that were able to differentiate into not just neurons and astrocytes, but also oligodendrocytes, which make the myelin that insulates nerve fibers and allows them to transmit signals. The scientists dubbed the newly converted population “induced neural precursor cells,” or iNPCs.

In addition to confirming that the astrocytes, neurons and oligodendrocytes were expressing the appropriate genes and that they resembled their naturally derived peers in both shape and function when grown in the laboratory, the researchers wanted to know how the iNPCs would react when transplanted into an animal. They injected them into the brains of newborn laboratory mice bred to lack the ability to myelinate neurons. After 10 weeks, Lujan found that the cells had differentiated into oligodendroytes and had begun to coat the animals' neurons with myelin.

“Not only do these cells appear functional in the laboratory, they also seem to be able to integrate appropriately in an in vivo animal model,” said Lujan.

The scientists are now working to replicate the work with skin cells from adult mice and humans, but Lujan emphasized that much more research is needed before any human transplantation experiments could be conducted. In the meantime, however, the ability to quickly and efficiently generate neural precursor cells that can be grown in the laboratory to mass quantities and maintained over time will be valuable in disease and drug-targeting studies.

“In addition to direct therapeutic application, these cells may be very useful to study human diseases in a laboratory dish or even following transplantation into a developing rodent brain,” said Wernig.

In addition to Wernig and Lujan, other Stanford researchers involved in the study include postdoctoral scholars Soham Chanda, PhD, and Henrik Ahlenius, PhD; and professor of molecular and cellular physiology Thomas Sudhof, MD.

The research was supported by the California Institute for Regenerative Medicine, the New York Stem Cell Foundation, the Ellison Medical Foundation, the Stinehart-Reed Foundation and the National Institutes of Health.

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The above story is reprinted from materials provided by Stanford University Medical Center. The original article was written by Krista Conger.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

E. Lujan, S. Chanda, H. Ahlenius, T. C. Sudhof, M. Wernig. Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1121003109

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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Contact: Krista Conger
kristac@stanford.edu
650-725-5371
Stanford University Medical Center

STANFORD, Calif. ? Mouse skin cells can be converted directly into cells that become the three main parts of the nervous system, according to researchers at the Stanford University School of Medicine. The finding is an extension of a previous study by the same group showing that mouse and human skin cells can be directly converted into functional neurons.

The multiple successes of the direct conversion method could refute the idea that pluripotency (a term that describes the ability of stem cells to become nearly any cell in the body) is necessary for a cell to transform from one cell type to another. Together, the results raise the possibility that embryonic stem cell research and another technique called “induced pluripotency” could be supplanted by a more direct way of generating specific types of cells for therapy or research.

This new study, which will be published online Jan. 30 in the Proceedings of the National Academy of Sciences, is a substantial advance over the previous paper in that it transforms the skin cells into neural precursor cells, as opposed to neurons. While neural precursor cells can differentiate into neurons, they can also become the two other main cell types in the nervous system: astrocytes and oligodendrocytes. In addition to their greater versatility, the newly derived neural precursor cells offer another advantage over neurons because they can be cultivated to large numbers in the laboratory ? a feature critical for their long-term usefulness in transplantation or drug screening.

In the study, the switch from skin to neural precursor cells occurred with high efficiency over a period of about three weeks after the addition of just three transcription factors. (In the previous study, a different combination of three transcription factors was used to generate mature neurons.) The finding implies that it may one day be possible to generate a variety of neural-system cells for transplantation that would perfectly match a human patient.

“We are thrilled about the prospects for potential medical use of these cells,” said Marius Wernig, MD, assistant professor of pathology and a member of Stanford's Institute for Stem Cell Biology and Regenerative Medicine. “We've shown the cells can integrate into a mouse brain and produce a missing protein important for the conduction of electrical signal by the neurons. This is important because the mouse model we used mimics that of a human genetic brain disease. However, more work needs to be done to generate similar cells from human skin cells and assess their safety and efficacy.”

Wernig is the senior author of the research. Graduate student Ernesto Lujan is the first author.

While much research has been devoted to harnessing the pluripotency of embryonic stem cells, taking those cells from an embryo and then implanting them in a patient could prove difficult because they would not match genetically. An alternative technique involves a concept called induced pluripotency, first described in 2006. In this approach, transcription factors are added to specialized cells like those found in skin to first drive them back along the developmental timeline to an undifferentiated stem-cell-like state. These “iPS cells” are then grown under a variety of conditions to induce them to re-specialize into many different cell types.

Scientists had thought that it was necessary for a cell to first enter an induced pluripotent state or for researchers to start with an embryonic stem cell, which is pluripotent by nature, before it could go on to become a new cell type. However, research from Wernig's laboratory in early 2010 showed that it was possible to directly convert one “adult” cell type to another with the application of specialized transcription factors, a process known as transdifferentiation.

Wernig and his colleagues first converted skin cells from an adult mouse to functional neurons (which they termed induced neuronal, or iN, cells), and then replicated the feat with human cells. In 2011 they showed that they could also directly convert liver cells into iN cells.

“Dr. Wernig's demonstration that fibroblasts can be converted into functional nerve cells opens the door to consider new ways to regenerate damaged neurons using cells surrounding the area of injury,” said pediatric cardiologist Deepak Srivastava, MD, who was not involved in these studies. “It also suggests that we may be able to transdifferentiate cells into other cell types.” Srivastava is the director of cardiovascular research at the Gladstone Institutes at the University of California-San Francisco. In 2010, Srivastava transdifferentiated mouse heart fibroblasts into beating heart muscle cells.

“Direct conversion has a number of advantages,” said Lujan. “It occurs with relatively high efficiency and it generates a fairly homogenous population of cells. In contrast, cells derived from iPS cells must be carefully screened to eliminate any remaining pluripotent cells or cells that can differentiate into different lineages.” Pluripotent cells can cause cancers when transplanted into animals or humans.

The lab's previous success converting skin cells into neurons spurred Wernig and Lujan to see if they could also generate the more-versatile neural precursor cells, or NPCs. To do so, they infected embryonic mouse skin cells ? a commonly used laboratory cell line ? with a virus encoding 11 transcription factors known to be expressed at high levels in NPCs. A little more than three weeks later, they saw that about 10 percent of the cells had begun to look and act like NPCs.

Repeated experiments allowed them to winnow the original panel of 11 transcription factors to just three: Brn2, Sox2 and FoxG1. (In contrast, the conversion of skin cells directly to functional neurons requires the transcription factors Brn2, Ascl1 and Myt1l.) Skin cells expressing these three transcription factors became neural precursor cells that were able to differentiate into not just neurons and astrocytes, but also oligodendrocytes, which make the myelin that insulates nerve fibers and allows them to transmit signals. The scientists dubbed the newly converted population “induced neural precursor cells,” or iNPCs.

In addition to confirming that the astrocytes, neurons and oligodendrocytes were expressing the appropriate genes and that they resembled their naturally derived peers in both shape and function when grown in the laboratory, the researchers wanted to know how the iNPCs would react when transplanted into an animal. They injected them into the brains of newborn laboratory mice bred to lack the ability to myelinate neurons. After 10 weeks, Lujan found that the cells had differentiated into oligodendroytes and had begun to coat the animals' neurons with myelin.

“Not only do these cells appear functional in the laboratory, they also seem to be able to integrate appropriately in an in vivo animal model,” said Lujan.

The scientists are now working to replicate the work with skin cells from adult mice and humans, but Lujan emphasized that much more research is needed before any human transplantation experiments could be conducted. In the meantime, however, the ability to quickly and efficiently generate neural precursor cells that can be grown in the laboratory to mass quantities and maintained over time will be valuable in disease and drug-targeting studies.

“In addition to direct therapeutic application, these cells may be very useful to study human diseases in a laboratory dish or even following transplantation into a developing rodent brain,” said Wernig.

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In addition to Wernig and Lujan, other Stanford researchers involved in the study include postdoctoral scholars Soham Chanda, PhD, and Henrik Ahlenius, PhD; and professor of molecular and cellular physiology Thomas Sudhof, MD.

The research was supported by the California Institute for Regenerative Medicine, the New York Stem Cell Foundation, the Ellison Medical Foundation, the Stinehart-Reed Foundation and the National Institutes of Health.

The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For information about all three, please visit http://stanfordmedicine.org/about/news.html.

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Stanford scientists turn skin cells into neural precusors, bypassing stem-cell stage