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Neuroscience, Stanford News, Stem Cells

Human neurons from skin cells without pluripotency?

Wernig pic for blog.JPGStanford scientists reached a milestone today with their publication in Nature of research showing that human skin cells can be converted directly into functional neurons. The research, which parallels an earlier study by the group on mouse skin cells, is notable because it skips what many stem cell experts used to think was a necessary step in the transformation – that of first treating the skin cells with a variety of factors to make them very developmentally flexible, or pluripotent. In our release, senior author and stem cell expert Marius Wernig, MD, describes:

We are now much closer to being able to mimic brain or neurological diseases in the laboratory. We may perhaps even be able to one day use these cells for human therapies.

Interestingly, this direct conversion technique may offer a way around the recently reported rejection of genetically identical iPS cells by laboratory mice. That unexpected finding, which I blogged about a couple of weeks ago, has researchers worried about the potential therapeutic value of the cells. But preliminary investigations suggested that the immune response was targeted at proteins used to make the original cells pluripotent, which shouldn’t be an issue with this approach. Wernig cautions against abandoning any one form of research, however:

The iPS cell approach is doable and has been shown to work. We need to keep working on both strategies. It’s possible that the best approach may vary depending on the disease or the type of research being done.

Previously: Stem cell breakthrough: Science over classical music, Setback for induced pluripotent stem cells, and Nature summarizes iPS cell challenges
Photo by Steve Fisch

In the News, Research, Science, Stem Cells

Nature summarizes iPS cell challenges

Nature summarizes iPS cell challenges

I wrote last week about disturbing results from scientists who found that iPS cells (also known as induced pluripotent stem cells) are attacked and rejected by the immune system of mice – even when the cells were genetically identical to the recipient animals. The finding illustrated how once-promising iPS cells – beloved among some political groups because they can be generated directly from a patient without destroying a human embryo – could face a rockier path to the clinic than most people first envisioned.

Reporter Erika Check Hayden outlines these and other challenges in today’s Nature News:

No one doubts that iPS cells still have enormous potential, but the field’s initial optimism has cooled. “Right now, we are a long way from being sophisticated enough to take advantage of these cells’ potential,” says neuroscientist Arnold Kriegstein of the University of California, San Francisco (UCSF). “Things are still at a very early stage.”

Erika goes on to discuss five major challenges, gathering input from many leading researchers, including our own Renee Reijo Pera, PhD. Erika is a fantastic reporter and it’s always a treat to read her thoughtful articles. You can also follow her on Twitter at @Erika_Check. I, for one, am going to bookmark the article for future re-reading and reference. There’s a lot to think about there.

Previously: Setback for induced pluripotent stem cells

In the News, Research, Stem Cells

Setback for induced pluripotent stem cells

Setback for induced pluripotent stem cells

A study (subscription required), just published in Nature by a group of researchers at UC-San Diego, suggests that the use of induced pluripotent stem cells, or iPS cells, for human therapy may be more problematic than previously thought. (iPS cells are cells reprogrammed from adult tissue to look and act like embryonic stem cells. The advantage of iPS cells lies in the fact that they aren’t made from embryos, and they will be a genetic match for the person who provided the original cells – presumably reducing or eliminating the chances of rejection by the immune system.) The researchers showed in laboratory mice that the animals rejected even genetically identical iPS cells. The reason seems to be that the animals’ immune systems were responding to at least one of the factors used to render the iPS cells pluripotent.

According to this just-posted New York Times article:

The initial creation of human iPS cells in 2007 electrified scientists because the cells seemed to have two big advantages over embryonic stem cells. They were not controversial, because their creation did not entail the destruction of human embryos. And since the stem cells could be made from a particular patient’s skin cells, they could be used to make tissues that presumably would not be rejected by that patient’s immune system.

But that latter assumption was never really tested, until now. When Yang Xu, a biologist at the University of California, San Diego, and colleagues did so, they found that iPS cells made from mouse skin cells were nonetheless rejected by genetically identical mice.

I had the opportunity yesterday to ask radiologist and stem cell researcher Joseph Wu, MD, about the study prior to its publication. Wu, who has published interesting work exploring ways to reduce the body’s immune response to embryonic stem cells, had this to say:

The overall significance of the finding is that more research needs to be done to examine whether or not iPS cells are immunoprivileged, or protected from an attack by the immune system. Are the findings in this study specific to the mouse iPSCs or will they also apply to human iPS cells? Will they also apply to differentiated iPS cells, which are more likely to be used in therapy? What is causing the rejection? Can we overcome it with advances in reprogramming techniques?

The research, and Wu’s questions, are fascinating. Obviously we don’t know all the answers yet. But it seems to validate the talking points of many stem cell researchers today, and that of the California Institute for Regenerative Medicine: It’s important to continue research on both iPS cells and embryonic stem cells because each form may have advantages and disadvantages that we haven’t yet identified.

Previously New technique prevents immune-system rejection of embryonic stem cells

Stanford News, Stem Cells

State stem cell institute awards funding to Stanford, Geron Corp.

Interesting news this morning from the California Institute for Regenerative Medicine. Not only did the institute’s governing board award four Stanford scientists a total of $5.7 million as part of their Basic Biology III Awards (congratulations to Michael Clarke, Renee Reijo Pera, Joseph Wu and Joanna Wysocka!), it also voted to fund Menlo Park-based Geron Corp‘s ongoing clinical trial of a human embryonic stem cell-based treatment for spinal cord injury – to the tune of $25 million. According to Robert Klein, the institute’s chairman:

Supporting the Geron trial is a landmark step for CIRM. However, we must remember that there will be successes and interim failures as human trials proceed through the refinements necessary to achieve a successful human therapy. We need to be prepared to stand by the heroic patients and the companies as they face these challenges and solve the problems that stand in the way of the recovery of patients from paralysis. When the people of California voted for proposition 71 they did so with the hope of seeing new therapies for disabling diseases like Alzheimer’s disease, Parkinson’s disease, diabetes and other chronic diseases and injuries. By funding this trial, CIRM is taking a major step toward making that hope a reality.

In January, Stanford and Santa Clara Valley Medical Center became the third site approved to participate in Geron’s phase-1 clinical trial of the cells. The first patient was treated in October 2010 at the Shepherd Center in Atlanta; Stanford has not yet treated a patient. Up to 10 patients will be enrolled during the first phase of the trial at seven sites nationwide.

With the addition of the Basic Biology III Awards, Stanford has now received about $192 million from CIRM – more than any other institution.

Previously Stanford joins first human embryonic stem cell trial

In the News, Research, Science Policy, Stem Cells

Stanford legal expert: Last Friday a “good day for embryonic stem cell research”

Stanford legal expert: Last Friday a "good day for embryonic stem cell research"

As reported here and elsewhere, a federal injunction banning federal funding for human embryonic stem cell research was overturned last Friday. For those of you interested in the legal details behind this development, Stanford law professor Hank Greely, JD, has written a lengthy and informative entry on the Law and Biosciences Blog. Greely’s conclusion?

April 29 was a good day for embryonic stem cell research. It has no immediate effect, as the injunction had been stayed, but it helps eliminate some of the legal uncertainty around this funding. It is not the end of the legal wrangling, but I think it greatly weakens the most serious legal challenge to this research.

Previously: Stem cell funding injunction overturned by federal court , Judge Lamberth’s stem cell opinion is disappointingly bad, More concern over US judge’s stem cell ruling and Stanford stem cell expert weighs in on district court ruling

Image of the Week, Stem Cells

Image of the Week: Motor neuron progenitors


Last Friday, the U.S. Court of Appeals overturned an injunction banning federal funding for human embryonic stem cell research. To celebrate this victory for biomedical research, here is a striking image from the California Institute for Regenerative Medicine Flickr photo stream showing motor neuron progenitors (marked in green) derived from human embryonic stem cells. Researchers are currently exploring methods for using such neurons to treat spinal cord injuries or neurological disorders including amyotrophic lateral sclerosis, commonly referred to as ALS or Lou Gehrig’s Disease.

The photo was taken by UC Irvine graduate student Sharyn Rossi at the Sue and Bill Gross Stem Cell Research Center.

Previously: Image of the Week: Marfan syndrome embryonic stem cell colonies, Image of the Week: Dopaminergic neurons derived from human embryonic stem cells and Image of the Week: neural stem cells

In the News, Science Policy, Stem Cells

Stem cell funding injunction overturned by federal court

Stem cell funding injunction overturned by federal court

Although it won’t knock the royal wedding off the charts as an attention getter for many people, I was excited to learn this morning that the U.S. Court of Appeals has overturned an injunction banning federal funding for human embryonic stem cell research. The injunction was issued last year by federal judge Royce Lamberth in response to a lawsuit by two researchers who argued that such funding was not only prohibited by the Dickey-Wicker amendment, but that it also put adult stem cell researchers at a disadvantage when competing for funds.

According to this morning’s blog post on Nature’s The Great Beyond:

The US Court of Appeals for the District of Columbia Circuit minutes ago vacated a lower court’s preliminary injunction blocking the National Institutes of Health (NIH) from funding human embryonic stem cell research.

In this 2-1 decision in Sherley et al v. Sebelius, the majority wrote that judge Royce Lamberth of the US District Court for the District of Columbia “abused [the court's] discretion” when he issued this preliminary injunction that shut down NIH funding of stem cell research for 17 days last summer.

Justices Douglas Ginsburg and Thomas Griffith, two of the three judges who heard arguments in the case in December argue that the plaintiffs, adult stem cell researchers, were less than persuasive in their contention that they were being harmed by competion with human embryonic stem cell researchers for NIH funding.

Ginsburg and Griffith also felt that the case was unlikely to succeed its merits, which is a legal prerequisite for such an injunction.

Although the injunction stopped federal funding for human embryonic stem cell research for over two weeks last August, the U.S. Court of Appeals issued a stay in September on the grounds that it would cause irreparable harm to ongoing research. Since then, researchers and ethicists have been awaiting a formal ruling. According to Nature:

While the preliminary injunction has now been vacated, a ruling on the substance of the case still rests with Judge Lamberth. Both sides have asked him to rule speedily on the matter.

Previously: Stanford stem cell expert weighs in on district court ruling, NIH intramural human embryonic stem cell research halted and U.S. Court of Appeals suspends ban on stem cell funding

Stanford News, Stem Cells

Stanford launches doctoral program in stem cell science

Updated 04-29-11: Here’s some very exciting news just out of the Faculty Senate:

Stanford University’s Faculty Senate has approved the creation of what officials believe is the first PhD program devoted solely to stem cell science in the nation and, perhaps, the world. The new doctoral program in stem cell biology and regenerative medicine is also the first interdisciplinary doctoral program created by the School of Medicine in recent years.

School officials say the fact that the university is taking the rare step of creating a new doctoral program acknowledges the growing importance of stem cell research in the realm of biomedical science. . . .

Autism, Stem Cells, Videos

Using stem cells to advance autism research

National Institute of Mental Health Director Thomas Insel, MD, recently interviewed Stanford neurobiologist Ricardo Dolmetsch, PhD, about his autism research involving induced pluripotent stem cells, which are created by reprogramming the gene expression patterns of specialized adult cells. In the video, Dolmetsch explains how he and colleagues devised a technique that allowed them to generate stem cells from children with autism and use these cells to create miniature brains in the lab. He also discusses how researchers are using this method to study brain function in children with autism and develop new therapeutics.

Previously: Valentine’s Day in a dish: heart cells made from skin cells help study, treat disease, Stanford Magazine spotlights scientists’ efforts to untangle the root causes of autism and Research on autism is moving in the right direction
Via Left Brain/Right Brain

NIH, Research, Stanford News, Stem Cells

Center for Reproductive and Stem Cell Biology receives NIH boost

Stanford’s Center for Reproductive and Stem Cell Biology has been awarded a $10 million grant from the National Institute of Child Health and Human Development. The grant is one of a select few intended to help institutions form “networks that foster communication, innovation and high-quality research in a particular area of science. They also provide a stimulating, multidisciplinary environment that attracts both established and promising new investigators.”

Stanford stem cell biologist Renee Reijo Pera, PhD, is the director of the center, which was launched last year. Other main participants are developmental biologist Margaret Fuller, PhD, and Aaron Hsueh, PhD, professor of obstetrics and gynecology. According to Reijo Pera:

One of the significant concepts behind this translational center is that we aim to take stem cell research results derived from model organisms, especially flies and mice, and translate our knowledge to applications in human health. Over the last 50 to 100 years we have amassed a backlog of exquisite basic science data describing germ line and embryo development that has not been applied to humans. We haven’t yet reached the promise for translating such findings to potential therapeutics and diagnostics.

The center is to be housed in the Lorry Lokey Stem Cell Building and will study some of the earliest events in development – in humans as well as lab animals – in an effort to advance human reproductive health. This grant is its first funding.

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