Category Archives: Stem Cell Research

The Hindu Prof. Shinya Yamanaka of Centre for iPS Cell Research and Application, Japan, delivering a lecture in New Delhi on Friday. Photo: R.V.Moorthy

Renowned Japanese scientist Shinya Yamanaka, who achieved a major breakthrough in the emerging area of stem cell research by creating a possible alternative to embryonic stem cells in 2007, expressed confidence here on Friday that drugs would be available soon for diseases for which therapies are yet to be found.

Delivering a lecture on “New Era of Medicine with iPS Cells” organised jointly by Cell Press and TNQ Books and Journals, Prof. Yamanaka said the cells -- “induced pluripotent stem cells [iPS Cells]'' -- developed by him and his team would not only help overcome the ethical issues surrounding use of embryonic stem cells for treatment of diseases like spinal cord injuries, Type I diabetes or macular diseases but also help in development of drugs for conditions like motor neuron disease.

Embryonic stem cell therapy is considered important as it offers immense possibilities for treatment of a wide range of diseases and conditions since the cells proliferaterapidly and are pluripotent or possess the capability to differentiate into any type of cell, said Prof. Yamanaka. But it suffers from a major ethical issue as it involves use of live human embryos, Prof. Yamanaka pointed out. He said if there was a post-transplant rejection, they cannot be used from the patient's own cell.The iPS cells, on the other hand, are created from adult skin cells and do not have these two problems, while at the same time they provide for rapid proliferation and the possibility to differentiate into any type of cell, he said. Prof. Yamanaka and his team generated iPS mouse cells in 2006 and followed up with iPS cells developed from human skin cells in 2007.

Speaking about the potentials of iPS cells, he said studies using the cells for treatment of spinal cord injuries have already shown good results in mouse and monkey specimens and in two to three years scientists would be ready to go in for clinical trials. He, however, admitted that there are several challenges before the new technology. Its safety is yet to be proved completely and the process of deriving patient-specific iPS cells is time-consuming and expensive.

He expressed hope that scientists who are working on itwould overcome the challenges and a new era in medical treatment would emerge soon.

Union Human Resource Development Minister Kapil Sibal, who introduced him, said his Ministry along with the Ministries of Health and Science & Technology would take steps for Indian scientists to collaborate with him.

TNQ Books and Journals Managing Director Mariam Ram and Cell Press Executive Editor Emilie Marcus also spoke.

The rest is here:
New era of medicine in the offing, says scientist

More than 250 participants, including key ethicists and scientists, will present their views on stem cell research and its ethics at the Qatar International Conference on Stem Cell Science and Policy due to take place in Doha this month.
More than 45 national, regional and international institutes have already submitted over 70 abstracts for the conference.
The abstracts examine the various challenges and opportunities that stem cell research presents, and include themes such as the therapeutic potential of stem cell research, the challenges presented by stem cell research in the context of the GCC region, the commercial applications of stem cell research, and one of the most important topics in the dialogue surrounding stem cell research – the ethics and its ramifications for stem cell guidelines and policies.
“This is a unique opportunity for Qatar Foundation to continue the open dialogue it has established through its partnership with James A Baker III Institute and the Qatar Faculty of Islamic Studies on ethics in stem cell research,” said Faisal Mohammed al-Suwaidi, president, research and development, at Qatar Foundation.
The conference is the culmination of a series of initiatives developed through this tripartite partnership to develop best ethical practice in stem cell research in Qatar and across the region, including workshops with religious scholars in 2009 and a public forum in May 2010.
“We want to raise awareness about Qatar’s developments in stem cell research; however, we also want to explore the ethical policy ramifications that come along with these developments. The conference will invite scientists, ethicists and policy makers across Qatar, the region and the world to address the issues surrounding stem cell research and develop policy recommendations that account for ethical, religious and cultural factors,” said Khaled al-Subai, director, research co-ordination and compliance, Qatar Foundation.

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Institutes submit papers for stem cell conference

(SACRAMENTO, Calif.) - Experts from UC Davis Health System will share the latest research about regenerative medicine, with a focus on chronic pain and the promise of stem cell therapies, during a community forum on the university's Sacramento campus. The discussion takes place on Tuesday, Feb. 7, from 6- 7:30 p.m. at the UC Davis Education Building, 4610 X Street, in Sacramento.

The event features Jan Nolta, director of the UC Davis Institute for Regenerative Cures; Scott Fishman, chief of the UC Davis Division of Pain Medicine; and Kee Kim, chief of spinal neurosurgery at UC Davis Medical Center. The three specialists will discuss the challenges of treating chronic pain, especially back and neck pain, and the clinical research now under way to use stem cell therapies to overcome it.

The forum is free and open to the public. It is part of "Stem Cell Dialogues," UC Davis Health System's discussion series about regenerative medicine and the goal of turning stem cells into cures. Each speaker will provide a short presentation followed by a panel discussion and question and answer period. The event will be moderated by Fred Meyers, professor of medicine and pathology, and executive associate dean of UC Davis School of Medicine.

Seating is limited. Those interested in attending must reserve a seat by contacting Kate Rodrigues at 916-734-9404 or e-mail kathleen.rodrigues@ucdmc.ucdavis.edu. Doors open at 5:30 p.m.  Free parking will be available in Lots 12 and 14, just south of the Education Building, near 45th Street and 2nd Avenue.

UC Davis is playing a leading role in regenerative medicine, with nearly 150 scientists working on a variety of stem cell-related research projects at campus locations in both Davis and Sacramento. The UC Davis Institute for Regenerative Cures, a facility supported by the California Institute for Regenerative Medicine (CIRM), opened in 2010 on the Sacramento campus. This $62 million facility is the university's hub for stem cell science. It includes Northern California's largest academic Good Manufacturing Practice laboratory, with state-of-the-art equipment and manufacturing rooms for cellular and gene therapies. UC Davis also has a Translational Human Embryonic Stem Cell Shared Research Facility in Davis and a collaborative partnership with the Institute for Pediatric Regenerative Medicine at Shriners Hospital for Children Northern California. All of the programs and facilities complement the university's Clinical and Translational Science Center, and focus on turning stem cells into cures. For more information, visit http://www.ucdmc.ucdavis.edu/stemcellresearch.

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The promise of stem cell therapies forum

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.

Original post:
Experimental Neurology Journal: BrainStorm's NurOwn™ Stem Cell Technology Shows Promise for Treating Huntington's ...

The stem cell stage was always thought to be a necessary step in the transformation of one type of cell into another, but new research from the Stanford University School of Medicine suggests that may not be the case. According to Medical News Today, scientists at the California school were able to successfully convert mouse skin cells directly into neural precursor cells, which then form the three main types of brain and nervous system cells.

“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,” said senior author Marius Wernig. “This is important because the mouse model we used mimics that of a human genetic brain disease.”

The same team had previously transformed mouse and human skin cells directly into functional neurons, but the new study is particularly exciting because of the possibilities neural precursor cells offer. While the cells can go on to become neurons, they can also differentiate into atrocytes and andoligodendrocytes, which maintain neurons and connect them to one another in order to transmit signals. Neural precursor cells are also easily stored in large numbers and better for lab work, the researchers noted.

If the implications of the research are correct and the stem cell stage is no longer necessary, controversial embryonic stem cell research may be needless. And not only would eliminating embryonic stem cell research avoid ethical questions, it would negate the need for stem cell patients to take drugs that stop their immune system from rejecting the foreign tissue. Wernig cautioned that further work is needed before these conclusions can be drawn, however. Researchers must still show that a similar cell conversion in humans is possible.

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Stem Cell Stage Bypassed in Skin Cell to Brain Cell Transformation

Halfway through its initial ten-year mandate, the California Institute for Regenerative Medicine (CIRM) in San Francisco is confronting a topic familiar to anyone at middle age: its own mortality.

The publicly funded institute, one of the world’s largest supporters of stem-cell research, was born from a state referendum in 2004. Endorsements from celebrities such as then-state governor Arnold Schwarzenegger and the late actor Christopher Reeve, who had been paralysed by a spinal injury, helped to garner voter support for a public bond to underwrite the institute. But with half of the US$3 billion that it received from the state now spent and the rest expected to run out by 2021, CIRM is now actively planning for a future that may not include any further state support.

“It would be premature to even consider another bond measure at this time,” wrote Jonathan Thomas, CIRM’s chairman, in a draft of a transition plan requested by the state legislature. Thomas outlined the plan on 24 January at a public hearing held in San Francisco by the US Institute of Medicine, which CIRM has asked to review its operations.

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.

“It would be a very different landscape if CIRM were not around.”

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.

CIRM is developing plans to help its grantees to continue their work if the agency closes. One option is a non-profit ‘venture philanthropy’ fund that would raise money from private sources to support stem-cell research. The agency is also writing a strat­egic plan for the rest of its ten-year mandate that focuses on translating research into the clinic, acknowledging that CIRM’s best shot at survival — and at sustaining future funding for stem-cell researchers — could come from a clinical success.

As CIRM board member Claire Pomeroy, chief executive of the University of California, Davis, Health System in Sacramento, noted at the agency’s board meeting on 17 January: “If you asked the public what they would define as success, they would say a patient benefited.”

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Stem-cell agency faces budget dilemma

JUPITER, Fla., Jan. 31, 2012 /PRNewswire/ -- BioRestorative Therapies, Inc. (OTCQB: BRTX) ("BRT") today announced that it has entered into a License Agreement with Regenerative Sciences, LLC ("RS") with respect to certain stem cell-related technology and clinical treatment procedures developed by RS. The treatment is an advanced stem cell injection procedure that may offer relief from lower back pain, buttock and leg pain, or numbness and tingling in the legs or feet as a result of bulging and herniated discs.

To date, over 40 procedures have been performed on patients. It is a minimally invasive out-patient procedure, and objective MRI data and patient outcomes for this novel injection procedure show positive results with limited patient downtime. BRT intends to utilize the existing treatment and outcome data, as well as further research, to prepare for clinical trials in the United States.

Pursuant to the agreement, BRT will obtain an exclusive license to utilize or sub-license a certain medical device for the administration of specific cells and/or cell products to the precise locations within the damaged disc and/or spine (and other parts of the body, if applicable) and an exclusive license to utilize or sublicense a certain method for culturing cells for use in repairing damaged areas. The agreement contemplates a closing of the license grant in March 2012, subject to the fulfillment of certain conditions. 

Mark Weinreb, Chairman and CEO of BRT, said, "This possible alternative to back surgery represents a large market for BRT once it begins offering the procedure to patients who might be facing spinal fusions or back surgery (which often times is unsuccessful). By delivering a particular cell population using a proprietary medical device that inserts a specialized needle into the disc and injects cells for repair and re-population, BRT hopes to revolutionize how degenerative disc disease will be treated." 

About BioRestorative Therapies, Inc.
BioRestorative Therapies, Inc.'s goal is to become a medical center of excellence using cell and tissue protocols, primarily involving a patient's own (autologous) adult stem cells (non-embryonic), allowing patients to undergo cellular-based treatments. In June 2011, the Company launched a technology that involves the use of a brown fat cell-based therapeutic/aesthetic program, known as the ThermoStem™ Program.  The ThermoStem™ Program will focus on treatments for obesity, weight loss, diabetes, hypertension, other metabolic disorders and cardiac deficiencies and will involve the study of stem cells, several genes, proteins and/or mechanisms that are related to these diseases and disorders.  As more and more cellular therapies become standard of care, the Company believes its strength will be its focus on the unity of medical and scientific explanations for clinical procedures and outcomes for future personal medical applications.  The Company also plans to offer and sell facial creams and products under the Stem Pearls™ brand.

This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events or results to differ materially from those projected in the forward-looking statements as a result of various factors and other risks, including those set forth in the Company's Form 10, as amended, filed with the Securities and Exchange Commission. You should consider these factors in evaluating the forward-looking statements included herein, and not place undue reliance on such statements. The forward-looking statements in this release are made as of the date hereof and the Company undertakes no obligation to update such statements.

CONTACT:  Mark Weinreb, CEO, Tel: (561) 904-6070, Fax: (561) 429-5684

Continued here:
BioRestorative Therapies Signs License Agreement for Stem Cell Disc/Spine Procedure

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.

Provided by Stanford University Medical Center (news : web)

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

Public release date: 30-Jan-2012
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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.

###

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.

PRINT MEDIA CONTACT: Krista Conger at (650) 725-5371 (kristac@stanford.edu)
BROADCAST MEDIA CONTACT: M.A. Malone at (650) 723-6912 (mamalone@stanford.edu)

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

(Photo: REUTERS/Shannon Stapleton)

U.S. Republican presidential candidate and former Speaker
of the House Newt Gingrich (R) speaks to the media after
attending a church service at the Exciting Idlewild
Baptist Church in Lutz, Florida January 29, 2012.

"I believe life begins at conception," the Republican
presidential hopeful stressed Sunday at a news conference
outside a Baptist church in Lutz, Fla.

"The question I was raising was what happens to embryos in
fertility clinics," Gingrich added, referring to the remarks he
made a day earlier at another Baptist church in Winter Park,
that embryonic stem-cell research amounts to "the use of
science to
desensitize society over the killing of babies."

Gingrich's proposal was seen as an attempt to woo evangelical
voters and gain an edge over former Mass. Gov. Mitt Romney, his biggest opponent in
Florida.

Gingrich went on to say he was in favor of a commission to
"look seriously" at the ethics of how fertility clinics are
managed. "If you have in vitro fertilization, you are creating
life; therefore, we should look seriously at what the rules
should be for clinics that are doing that, because they are
creating life," The Associated Press quoted him as saying
outside Exciting Idlewild Baptist Church.

Gingrich, who vocally supported federally funded research about
a decade ago, said he was also against the use of leftover
embryos for stem cell research.

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In vitro fertilization or IVF refers to formation of an embryo
outside a woman's body for implant inside the womb. Human
embryos can also be used in treatment or cure of illnesses and
injuries but they have life, conservatives say.

In 2009, President Barack Obama lifted restrictions on federal
funding for stem cell research, which were put in place by his
predecessor, George W. Bush in 2001.

Romney, who is not against the use of stem cell research on
excess embryos in fertility clinics, is leading in polls in
Florida. Reuters/Ipsos online poll results released Sunday
showed Romney having the support of 42 percent of likely voters
while Gingrich's support stood at 30 percent.

"It's clear that Romney's run a much more focused and effective
campaign in Florida than Newt," Republican strategist Matt
Mackowiak said Sunday, according to Reuters. "Newt's playing
defense every single day in every way and doesn't seem to be
able to make Romney play defense."

Excerpt from:
Gingrich Vows to Ban Embryonic Stem Cell Research