Goodbye from Nature Reports Stem Cells

We are sad to announce that Nature Reports Stem Cells is closing down.

When we launched in June 2007, we wanted to support the stem cell field and the interested public by providing freely available content. Stem cell research was then – and is still – exciting and expanding. It requires highly varied experts to think and work together, and it requires the support and understanding of non-scientists. We believe we have been successful in creating a venue that highlights and explores the many facets and implications of stem cell science. It is now time for us to move on to fresh publishing challenges.

We have been helped by many contributors and experts who have generously given their time and insight. We give a heartfelt thanks to everyone who wrote articles or gave interviews, advice, and words of encouragement.

NRSC and this blog will continue to remain online as an archive. Nature and its sister titles remain committed, as ever, to publishing new research and news about stem cells.

Monya Baker, Editor

Natalie DeWitt, Editor at Large

Stanford conference: stem cells, the new NIH, and delimiting embryo research

Students from the law and medical schools at Stanford University brought together an impressive group of world-class experts last week to discuss stem cell policy. I’ll describe some (very select) highlights over the next few blogs. Check the site for the Stanford Journal of Law Science & Policy over the next few weeks for powerpoints presentations and audiorecordings.

The people who will assess which human embryonic stem cell lines should be eligible for U.S. federal funding will meet next week, said Story Landis, head of the Stem Cell Task Force at the U.S. National Institutes of Health. In March this year, President Barack Obama charged the NIH with crafting policy to allow the funding of responsible embryonic stem cell research. In July, the NIH declared that this would include cell lines created from embryos made for reproductive purposes and donated without financial inducements and with proper informed consent. Determining proper informed consent is a bit of a minefield, particularly for embryos donated in the 1990s, before much of the debate and consensus-building around the issue occurred. See Stem cell vetting raises concerns, confusion

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Stanford conference: patient-heroes of clinical research

“When you think you have a policy, you’re too late.” That’s the opinion of Pearl O’Rourke, who directs human research affairs at Partner Healthcare Systems She was referring to the pace of research in the stem cell field and the need to fashion policies to protect subjects. Embryonic stem cell research oversight committees are becoming too much of a catchall, she worries.

Insoo Hyun, of Case Western Reserve University, said that the ethical considerations for stem cell–based clinical trials were similar to those for other experimental procedures but with the “heat” turned up — patients are more desperate, procedures are riskier, snake-oil salesmen more of a factor and slots in research trials are fewer. Outside clinical trials, perhaps some of the thinking developed for assessing new surgical techniques could be useful. Organ transplants, after all, did not go through clinical trials. Thomas Okarma, president and CEO of Geron, which is developing an embryonic stem cell product for spinal cord injury, described how he thought the cells might work (one mechanism is the secretion of various health factors, which could have implications for stroke and Alzheimer’s disease). At the same time, he said his company is committed to “maintain[ing] a conservative risk-benefit calculus”, which basically means only trying the riskiest therapies in very ill patients with very few other options, thus reducing the potential to harm patients.

Stanford University’s Hank Greely shared a few thoughts to guide this kind of analysis. Regulators demand that research be safe, but the very uncertainty makes this impossible, he said. That, in a sense, makes those who participate in Phase I trials heroes. No one can be certain what will happen when some new therapy or procedure is tried in humans. And consent is particularly important when the risk is high, he said, indicating that risky procedures should be tested in adult patients before children, even if a procedure is more likely to work in a younger population.

Finally, he lamented the fact that because conversations between regulatory authorities and clinical trial sponsors are confidential, crucial risk-reducing, therapy-speeding knowledge does not spread freely. He called on those involved to reveal the thinking behind regulatory decisions.

Editor’s note: Students from the law and medical schools at Stanford University brought together an impressive group of world-class experts last week to discuss stem cell policy. I’ll describe some (very select) highlights over three blogs. Check the site for the Stanford Journal of Law Science & Policy over the next few weeks for powerpoints presentations and audiorecordings.

Stanford conference: Geron’s 345 patents and reasons for stem cell intellectual property

Perhaps more confusing than making and using stem cells are the intellectual property rules governing such use. In addition to the licenses his company has attained from the Wisconsin Alumni Research Foundation, David Earp, patent counsel for Geron, said that his company had filed more than 300 patents covering a variety of areas: undifferentiated cells; differentiated cells; methods to scale, differentiate and process cells; and ways to grow cells without blood products and feeder layers.

Esther Kepplinger of the law firm Wilson Sonsini Goodrich & Rosati and Robin Feldman of the University of California Hastings College of the Law provided a stem cell–focused tutorial on what criteria a valid patent must establish and what areas a patent can cover. For instance, a patent can cover the cells themselves, the method of producing the cells or the use of cells in therapy or diagnosis.

Kepplinger, who oversaw the assessment of patents at the U.S. Patent and Trademark Office before joining the law firm, said that from what she’s seen, the patent office is rejecting more patents and claims have been getting narrower. She also said that because stem cell patents are likely to be of high public interest, they can receive extra scrutiny. Finally, she defended the existence of patents themselves: without them, she said, companies would not make the necessary investments to develop new products.

Aurora Plomer, of the University of Sheffield Law School, described what she considers a sort of drift of the European Patent Office’s directive declaring that uses of human embryos for industrial or commercial purposes are not patentable. The intention of the directive was to prevent fertility clinics from turning embryos into commodities. The interpretation of the directive to cover embryonic stem cells, products made from embryonic stem cells and products made with research using embryonic stem cells is highly flawed, she says.

Editor’s note: Students from the law and medical schools at Stanford University brought together an impressive group of world-class experts last week to discuss stem cell policy. I’ll describe some (very select) highlights over three blogs. Check the site for the Stanford Journal of Law Science & Policy over the next few weeks for powerpoints presentations and audiorecordings.

A small molecule replaces Sox2, and honors baseball

The standard technique for creating make differentiated cells behave like embryonic stem cells uses viruses to insert the genes cMyc, Klf4, Oct4, and Sox2 into cells, but adding these genes to cells makes them less predictable and more likely to form tumors. Researchers have been able to reprogram neural stem cell using only Oct4, but these cells are not readily available from patient biopsies and so researchers are searching for alternate techniques. New work published in Cell Stem Cell shows that a small druglike molecule can effectively replace two of the four genes typically used to generate induced pluriptotent stem cells.

To begin their hunt for compounds that could help reprogram cells, researchers led by Kevin Eggan and Lee Rubin of the Harvard Stem Cell Institute used cultures of mouse skin cells engineered to express green fluorescent protein as a marker of pluripotency. They first screened for small molecules that allowed mouse cells to be reprogrammed without adding the gene for Sox2. When three such molecules were identified, the researchers tried again and found that one of the molecules could reprogram cells even in the absence of cMyc, a tumour-promoting gene that, while not required for reprogramming, greatly boosts reprogramming rates.

To make sure the cells were really reprogrammed, the researchers performed a series of tests, including mixing them with mouse embryos and demonstrating that they could contribute to every type of tissue in chimeric mice. They named the identified molecule RepSox for its ability to replace Sox2 and also after the Red Sox, the local baseball team. Previous studies had identified this molecule as inhibiting a pathway known as TGF-beta signaling. Careful work showed that RepSox did not work by activating the Sox2 gene in fibroblasts, as might be expected. Instead, the molecule functions in partially reprogrammed cells that accumulate in the absence of Sox2, apparently by inducing and stabilizing Nanog expression. Thus, the researchers write, the discovery of RepSox is important not only for replacing one of the reprogramming factors but for illuminating a new strategy to identifying such molecules. “There need not always be a discrete, one-to-one mapping between the functions of the reprogramming factors and their chemical replacements.”

Robert Blelloch, who studies reprogramming at the University of California San Francisco, praised the team’s strategy of only screening compounds whose mechanisms are at least partly understood. “They find a small molecule that replaces a factor, but they take it further and use it to understand the biology.”

See also: Induced pluripotent stem cells: down to one factor

Notes on a neural stem cell conference

Editor’s note: The stem cell world has been rich with conferences in the past week or so. I hope to have very brief notes on Cold Spring Harbor Laboratory and Stanford’s interdisciplinary program on stem cell policy over the next few days. For the recent World Stem Cell Conference in Baltimore, please check for Elie Dolgin’s posts in In the Field.

The conference report below comes from Julie Clark, a scientist at Stemgent, who had previously covered the ISSCR conference for the Niche, and volunteered again. Thanks very much to Julie! —Monya

UCSF began October with its 2nd International Stem Cell Symposium: Frontiers in Neural Stem Cells . The planning committee brought together 23 of the leading authorities in neuroscience and made available a real-time symposium blog (http://nscmeeting.blogspot.com/) to facilitate Q&A.

With the possibility of cell replacement therapy on the horizon, this symposium probed how neural stem cells function in brain development and repair.

The origin of neural stem cells and building and repairing the cortex were the emphasis of the first of this two day symposium. Here are a few highlights.

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Ideas on stem cells: consent, use, nature

Earlier this month, the NIH assembled a working group to decide whether currently existing human embryonic stem cell lines confirm with the spirit of guidelines released on July 7. (See Let the vetting begin ) Much of the assessment will center on informed consent procedures.

Today, Bernard Lo well-known member of that working group has correspondence in Nature regarding how informed consent should be obtained for collecting tissue for creating human induced pluripotent stem cells. In it, Lo and Bruce Conklin, both at the University of California, San Francisco call for scientists to develop basic rules that donors should agree to. Other correspondence from scholars at the University of Sydney calls for informed consent to be local.

Elsewhere, Lee Buckler of the Cell Therapy Blog laments a poll showing that many science-savvy readers (and, apparently writers at Genetic Engineering News) are unaware that adult stem cells are being tested in clinical trials.

In an interview with The Scientist, Arthur Lawler argues that researchers will not be able to home in on a single molecular network of stemness, and so the concept of cells could be more profitably pursued in the context of their own tissues rather than overarching ideas. “It’s a system level property,” Lander says, “so we need to have information about a whole system.”

For more on that see Nature Reports’ commentary, Stem cell: what’s in a name?, and our interview with Irv Weissman, in which he calls for the creation of stem cell departments. Ironically, I’m not sure anyone is fundamentally disagreeing so much as using different words to grope at similar ideas.

More stem cells in Lou Gehrig’s disease

Shortly after my coverage of the FDA’s approval for NeuralStem’s stem-cell trial for amyotrophic lateral sclerosis appeared on the Niche, Letizia Mazzini and Franca Fagioli of Eastern Piedmont University contacted me to tell me about their team’s work using mesenchymal stem cells for the same disease. While Neuralstem is moving forward with neural stem cells, Mazzini and colleagues have been exploring the use of mesenchymal stem cells derived from the patient who will receive them. She has recently published results of a Phase I trial as well as a review of stem-cell approaches in ALS. Unfortunately, I learned of this work only after I’d posted.

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88 stem cell lines submitted to NIH for ethical vetting; Harvard dominates

As of 28 Sept in California, 88 human embryonic stem cell lines on a list the NIH is keeping to which institutions plan to submit which lines for an assessment of their eligibility for federal funding.

On July 7, the NIH specified strict informed consent and other criteria under which embryonic stem cell lines must be derived to be eligible for U.S. federal funding. Rather than having to meet the exact criteria of new informed consent requirements, lines derived prior to July 7 must be evaluated individually to ensure that they confirm to the principles behind the guidelines.

All but three lines are from Harvard University and its affiliated Children’s Hospital Boston; two are from Rockefeller University in New York, and one is from Children’s Memorial Hospital in Chicago. Notably absent are lines from the California universities and the University of Wisconsin. Also absent are lines derived outside the United States. However, Glyn Stacey, head of the UK Stem Cell Bank says that he believes that the guidelines on informed consent established among various groups in the UK complies with that set forward by the NIH. That was published last year in Regenerative Medicine (subscription required).

The list indicates an intent to submit rather than a formal submission, which will require substantial documentation.

See Stem cell vetting raises concerns, confusion

Stem cell vetting raises concerns, confusion

After years hearing scientists complain that the U.S. federal government funded research on too few human embryonic stem cell lines, Lana Skirboll, who directs the Office of Science Policy at the U.S. National Institutes of Health, has something to tell the stem cell community: “the ball is in their court.” The NIH announced on Monday that it would be accepting applications to determine whether a line is eligible for funding. The process is not without risks: some scientists are quietly concerned that their informed consent procedures could come under criticism, or that they could lose access to non-federal sources of funding if the lines they wish to work with aren’t cleared by the NIH.

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