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

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

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.

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.

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

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.

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.

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

The International Society for Stem Cell Research (ISSCR) has convened a new committee tasked with weeding out companies that offer unapproved stem cell 'therapies', the ISSCR's new president Irving Weissman announced today at the World Stem Cell Summit in Baltimore, Maryland.

See also an analysis of why unproven, risky stem-cell procedures elude legal restrictions in countries like China, India, Thailand, and the United States.

Last month, Weissman, who also directs the Stanford Institute for Stem Cell Biology and Regenerative Medicine in Palo Alto, California, wrote an opinion article in Cell Stem Cell calling for stem cell purveyors to be judged on three criteria. First, the company should be able to cite peer-reviewed papers from third party investigators showing that the therapy is possible. Second, there should be institutional review board oversight of the treatment. Third, the US Food and Drug Administration or an equivalent agency should give the final green light. "That's the minimum beginning," he said at the meeting.

Weissman revealed that he had convened an 18-member panel of lawyers, FDA regulators, medical ethicists, and stem cell scientists last week to look into the feasibility of establishing an online registry of wayward companies. His idea is for the ISSCR supervisory body to request documentation of the three requirements from all known global stem cell providers. Companies that don't comply would get blacklisted.

Weissman expects the committee to issue a preliminary report in December, with final guidelines published next March.

Image of Weissman by Kris Novak

See an interview Irving Weissman: culturing the unorthodox

After the fanfare surrounding President Barack Obama's executive order on 9 March, which lifted Bush-era restrictions on funding human embryonic stem cell research, the White House has been noticeably quiet about further expanding the science — one of Obama's campaign promises. "We need to remind the President of this type of research," Delaware congressman Michael Castle (Republican) said today at the World Stem Cell Summit in Baltimore, Maryland, the fifth annual summit presented by the non-profit Wellington, Florida-based Genetics Policy Institute.

Castle, together with Colorado congresswoman Diana DeGette (Democrat), previously introduced two bills to expand researchers' access to human embryonic stem cell lines. Both bills were approved by Congress but vetoed by former President George W. Bush. Now, both House Representatives are at it again, working on new legislation to augment the executive order and prevent potential policy reversals from future residents of 1600 Pennsylvania Avenue. "I don't like to see science subject to the whim of politics at all," said Castle, who is also working to overturn the Dickey-Wicker amendment, which forbids the creation of embryos for research purposes on the taxpayer's dime.

The bill is unlikely to brought before Congress anytime this year, however. Olivia Kurtz, Castle's senior legislative assistant, told me that Castle and DeGette hope to roll out the bill before the current Congress's term ends in January 2011. In the meantime, they are watching what happens with the National Institutes of Health's expanded guidelines to identify potential shortfalls in the executive order that need remedying. Castle singled out nuclear cloning — the technique that produced Dolly the sheep — as one line of research that deserves further attention.

Though both trials involve placing cells into the spinal cord, NeuralStem’s product is made of cultured neural stem cells derived from a single 8-week fetus; Geron’s product, intended to treat spinal cord injury, is derived from embryonic stem cells that have been differentiated into precursors of neuron-support cells.

“This is certainly the first stem-cell approach for ALS,” says Lucie Bruijn, a scientist at the ALS Association, a patient group that also funds relevant research. Most other approaches for treating ALS are small molecule drugs, she says, and she’s not aware of other cell therapy or other invasive approaches entering human testing in the near future.

ALS has not funded NeuralStem’s work directly, Bruijn says, but has advised the company and funded academic scientists who’ve been involved with the company.

NeuralStem’s chief scientific officer Karl Johe says tests of large animal models show that the transplanted cells exert a neuroprotective effect over motor neurons, but it’s not entirely clear how. Earlier this year, Neuralstem and collaborators published results in a rat model of ALS showing that transplanted cells could develop into interneurons that formed synapses with the rats’ motor neurons.

However, Johe emphasized that the upcoming trial will assess safety rather than efficacy. The first few patients selected for the procedure will be those who are no longer able to walk. Because the injected cells protect rather than replace motor neurons, these sicker patients are less likely to benefit from treatment, but they are less able to lose function if something goes wrong. Cells will be injected only on one side of the spinal cord in order to minimize the number of injections into the spinal cord. Only one patient will be injected each month, so that researchers can monitor for effects over a longer period. Eventually, Johe says, the goal is to be able to inject cells in both lower and upper regions of the spinal cord in healthier patients, and see if the injections can keep motor neurons healthy.

The trial is expected to take place at Emory University in Atlanta, Georgia. Though the FDA is allowing the trial to go forward, the university’s patient-safety board will also need to approve the trial before it can proceed. Johe declined to say when that would be but said discussions were well underway.

Other companies using neural cells include ReNeuron, which received permission from UK authorities this January to start clinical trials for stroke. Its cell product is made from genetically modified cultures of neural stem cells, also of fetal origin.

StemCells Inc is conducting trials in Batten’s disease, a neurodegenerative disease that strikes children, and recently received approval for a clinical trial for a similar disease. It also uses neural stem cells from material originally derived from fetuses and has recently published results showing that its cell product delayed some symptoms of the disease by about three weeks.

As with human embryonic stem cells, the patent situation for neural stem cells is contentious. In a pair of dueling press releases this May, NeuralStem and Stem Cells Inc both claimed key intellectual property on these cells.

The National Institutes of Health started accepting applications today to evaluate which human embryonic stem cells will be eligible for federal dollars.

A panel of nine scientists, lawyers and ethicists — led by Jeffrey Botkin of the University of Utah — will scrutinize submissions to ensure that they meet the new requirements for informed consent from embryo donors. The working group's "expertise and sound judgment will help NIH move forward in this important effort," NIH director Francis Collins, who will have the final say on the eligibility of particular lines, said in a statement.

The panel will review cell lines made before the guidelines went into effect on 7 July. Fundable lines must be derived from leftover embryos that were created solely for assisted reproduction and donated voluntarily with no financial incentives.

"We're open for business in a new era," Lana Skirboll, director of policy at NIH, told Nature. The working group has not yet appraised any cell lines — including the 21 lines approved under former President George W. Bush, which will need to be reassessed — and will start considering particular cells after scientists submit their petitions on the NIH website. "The speed at which this moves is really in the hands of the scientific community at this point," she said.

Having a mechanism in place to expand the number of eligible cell lines "is what we've been working toward for a very long time," said M. William Lensch, a stem cell researcher at Children's Hospital Boston and the Harvard Medical School, who expects to start submitting requests "sooner rather than later."

Image: James Thomson, University of Wisconsin-Madison

Editor's note:
(See related story: An analysis suggesting that the NIH did not properly evaluate informed consent by donors of embryos from which stem cell lines were derived throw oversight committees into disarray )

Also, see below a list of the other members of the panel and for links to a critical analysis of the ethical review conducted under President George W. Bush's administration.

(See CIRM’s melting pot of collaborators)

At a signing ceremony in CIRM’s office in San Francisco, the German Federal Ministry of Education and Research, Freider Meyer-Krahmer described the new memorandum of understanding as opening up “totally new ways of collaboration” with perhaps three or more countries coming together. “Not just the researchers but also the funders collaborate.”

CIRM president Alan Trounson said the agreement grew out of past meetings between German and Californian scientists who had identified ways that they wanted to work together, particularly on ways to understand how transplanted cells will interact with patients’ immune system. Officials declined to state the amount of funds that would be involved, but Trounson said that governments must commit a certain minimum amount of funds, on the order of $1 million to $2 million dollars to “make the paperwork worthwhile.”

The officials said that the collaboration would avoid duplication and allow researchers to capitalize on advantages within both jurisdictions. Both Trounson and CIRM chair Robert Klein praised German work conducting large clinical trials in adult stem cells.

Each government will conduct their own ratings of the submitted grants, said officials, but they would establish a mechanism to make sure that both CIRM and German granting agencies would be awarding grants to the same teams.

CIRM plans to pursue additional agreements in the near future, particularly with U.S. state governments that have allocated funds to stem cell research. Agreements are already in place with Australia, Canada, Japan, Spain, and the United Kingdom.