The Niche

A new paper in Cell Stem Cell describes how scientists reprogrammed human cells to pluripotency without using any DNA at all. Instead, reprogramming proteins were engineered so that they could enter the nucleus. These proteins were produced in cultures of mammalian cells and secreted into the culture media. When fibroblasts derived from newborns were exposed to those cell extracts, the cells reprogrammed to teratoma-producing induced pluripotent stem (iPS) cells, a big first for human cells.

Nature’s David Cyranoski covered the story for Nature News, and he generously provided some outtakes of quotes from his reporting, although even these are condensed from what he provided. His original notes were over ten pages!

Those quoted include several well-known experts:

The scientists who led the most-recent work: Kwang-Soo Kim of CHA Stem Cell Institute in Seoul, South Korea, and Harvard Medical School in Cambridge, Massachusetts; Robert Lanza, chief scientific officer of Advanced Cell Technology in Santa Monica, California.

The scientists who, among other work, reported protein-only reprogramming in mouse cells in April: Sheng Ding of The Scripps Research Institute in La Jolla, California; Hans Schöler of the Max Planck Institute for Molecular Biomedicine in Münster, Germany.

Outside experts: James Thomson of the University of Wisconsin–Madison, the first to derive human embryonic stem cells and human iPS cells; Shinya Yamanaka of Kyoto University, Japan, and the Gladstone Institute in San Francisco, the first to reprogram both mouse and human cells.

Below, they all discuss the significance of the results and hurdles ahead, the differences between the human and mouse techniques and the need to compare different cells.

Continue reading "Gene-free reprogramming in human cells" »

Posted by Monya Baker on May 28, 2009
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A patient death from unknown causes has led the company Aastrom to halt its clinical trial in which a mixed population of bone marrow cells is injected into patients’ heart muscle. The trial uses cells collected from the same patient who will receive the injection, and was examining the potential to treat heart failure caused by dilated cardiac myopathy.

Here is the press release from Aastrom. Here’s what's essentially a shortened version from Reuter’s.

There are a lot of trials using a patient’s own stem cells to treat heart disease; so far they don’t seem to do much benefit, but they don’t seem to cause harm either. See our 2008 feature, Stem cells for the heart, a new wave of clinical trials.

Aastrom’s is an unusual delivery method in injecting the cells right into the heart muscle, and it looked like it was gaining traction. See this report in the Times of India, which doesn’t mention Aastrom, but does refer to an affiliated scientist, Amit Patel. Patel gave the rosy update on Aastrom’s clinical trial on May 5th, a couple weeks before the death was announced. At that point, 13 of a desired total of 40 patients had been enrolled in the trial.

This year, there have been some positive results from Osiris and new approaches using sorted cells announced for using stem cells in heart failure.

Still, scientists have expressed strong doubts about whether bone-marrow derived cells will provide lasting benefits in heart failure. (See Q&A with Christine Mummery)

Posted by Monya Baker on May 22, 2009
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NOTE: The original posting of this blog contained an error about the 1999 NIH draft guidelines. That has been corrected.
All of you reading the hysteria about the decline of U.S. federal funding for human embryonic stem cells, please take a deep breath. Okay?

The NIH is seeking comment on draft guidelines, not seeking to stop embryonic stem cell research on all old lines. It's even unclear whether the draft guidelines would prohibit research on all the old Presidential lines, as the headlines state.

I’ve been reading the most recent media coverage (Here’s Wired and the Scientist ) in the wake of the commentary by Patrick Taylor in Cell Stem Cell, and I’ve yet to find a researcher who says explicitly that she or he thinks the majority of already extant cell lines will actually be excluded in the final guidelines because researchers didn’t have up-to snuff consent forms. Instead, my guess is, the NIH and stem cell community will have to either 1) laboriously work out whether the consent process used well in the past is sufficiently consistent with that in place now or 2) grandfather in the lines which the NIH had determined in 2001 to have been obtained with proper informed consent. (An analysis published last year found that not all of these lines met such standards and sent institutional review boards into disarray. Read more about that .)

My guess is that people want the NIH to say explicitly which lines can be used so that individual institutions don’t have to hash this through individually, a situation that will cause many people to do redundant work and could result in chaos. In fact, such explictness is one of the requests made explicitly in the template letter provided by the ISSCR.

The broader issues, of course, are whether the NIH will allow funding for lines derived from unfertilized eggs or from embryos created by nuclear transfer, or cloning. The first time the NIH drew up draft guidelines was for President Bill Clinton. Those guidelines did not allow research on embryos, but did allow research on embryonic stem cells created from embryos originally created for purposes of reproduction. (There were some other restrictions as well; see the 1999 draft guidelines). Then there was public comment, then the NIH changed the guidelines to restrict funding to lines from embryos created for reproductive purposes. The upshot of all this, tell the NIH what you think about human embryonic stem cell research by May 26, when the time for public comments close. (You can do that here . I wrote up a summary of the guidelines here.)

Taylor’s commentary is not about whether a specific line should or shouldn’t be used but about the approach that should be taken to informed consent. Put simply, he says, standards evolve constantly, so materials collected in the past should be evaluated according to the standards of that time. He then sets out a thought experiment to show what could happen if standards are applied retrospectively.

Another relevant thought experiment might be what could happen if the scientific community does not weigh in on setting the guidelines that it will need to live by. Hopefully that is not an experiment that will play out in real life. The comment form is here .

Posted by Monya Baker on May 20, 2009
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Of all the stem cells, I find skin stem cells the most confusing. So, I was really grateful for Elaine Fuchs and Cedric Blanplain's review in Nature Reivews Molceular Cell Biology. This week, we have a two-part Q&A with Fuchs about navigating a scientific career when she had few female colleagues and about loving the complexity of skin.

Besides our interview with Fuchs, we have a few highlights:
One discusses recent work by Rudolf Jaenisch published in Cell Stem Cell.
Another sheds some light on how pluripotency is controlled.
A third highlight talks about the surprisingly high occurrence of chromosomal abnormalities in embryos donated for research.

Elsewhere in NPG:
Stem cell regulations are coming under scrutiny in China, as reported in Nature.
A stem-cell researcher considers an accusation of dullness.
A brief research highlight in Nature talks about an infrared-emitting protein that can image intact animals and might be useful in stem cell research.
Last week, the CIRM approved $67.7 million to fund 15 grants focused on early translational stem cell research, and SciBX provided some details.

Enjoy! If you have any links to news articles or research highlights I may have missed, feel free to leave a comment or shoot me an e-mail.

Posted by Monya Baker on May 14, 2009
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Here's a highlight for research published in Cell and Nature:

Beating heart triggers blood stem cells in the embryo

Embryonic haematopoiesis needs flow, nitric oxide signalling

Blood stem cells are born just outside the embryonic heart. Though this fact is well known, the reasons behind it have posed a persistent mystery. Now two strands of research, one starting with embryonic stem cells, another with zebrafish, provide big clues. The solution may help researchers create a useful but elusive cell — the haematopoietic stem cells capable of replenishing an entire blood system.

The work, led by two teams of researchers from Harvard University, shows that haematopoietic stem cells form best under stress — more specifically, under the strain exerted by moving fluid, the flow created by a beating heart.

Continue reading "Beating heart triggers blood stem cells in the embryo" »

Posted by Monya Baker on May 14, 2009
Categories: Blood stem cells | Permalink | Comments (0) | TrackBacks (0)

Novocell, a San Diego company developing stem-cell technology for treating diabetes, has named its new CEO. John West has previously held management posts at Applied Biosystems. He was CEO of DNA sequencing company Solexa, until he sold it to Illumina for $600 million. (See the Novocell’s announcement and the San Diego Tribune article.

Novocell’s previous CEO, Alan Lewis, left last year to head the Juvenile Diabetes Research Foundation, which has awarded more than $1.3 billion to diabetes research, including $156 million last year. (According to the organization’s factsheet ) He had previously held leadership positions and Wyeth and Signal Pharmaceuticals and Celgene. His analysis of the stem-cell industry is recounted in our feature In search of a viable business model.

Here is an announcement of John West’s appointment as CEO in 2004 and a press release of John West’s resignation as VP of Sequencing at Illumina in February 2008.

So, why did one of the embryonic-stem-cell companies closest to developing cell therapy pick a CEO that has successfully run technology companies?

One idea is that the DNA-sequencing field is crowded and required some partnership. Another is that Novocell’s investors feel ready for its sale. After all, NovoNordisk announced a diabetes deal with stem-cell company Cellartis last year. And in April, Pfizer announced that it would be putting $100 million into its own stem cell research. The last funding round for Novocell that I could Google was for $25 million in 2007.

I know I have some industry-savvy readers, so if you send me good links and comments, I’ll post them. (It might take a couple days, as I’m travelling.)

Posted by Monya Baker on May 13, 2009
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Pfizer’s stem cell moves gets eyeballs
Just a couple weeks after announcing its plan to use stem cells to treat blindness, Pfizer announced it was putting $100 million into stem cell research, including the blindness project with University College London (UCL). (See the story in Business Weekly) The Pfizer Regenerative Medicine Unit plans to hire about 15 scientists at its Cambridge, UK location, so a total of up to 70 workers at its locations in Cambridge, UK and Cambridge, Massachusetts.
In April, the Times Online, along with other outlets, carried the story that it would be funding the UCL's efforts to cure macular degeneration with techniques that convert embryonic stem cells to retinal pigment epithelium cells. UCL scientists said they might be able to start human testing by 2012, and so stall one of the most common causes of blindness, and enter a lucrative market.
($100 million isn’t much compared to Pfizer’s approximately $8 billion research and development budget, but it’s a lot more than the $3 million given to finance EyeCyte, a bone-marrow cell therapy company, in June last year. Read more.)
An aside: Work at an earlier stage from Sheffield University describes transforming fetal stem cells into auditory neurons for potential transplantation to people suffering hearing loss. (See story from Reuters )

A day after disclosing a $4 million private placement, Cytori and GE Healthcare announced plans to commercialize Cytori’s equipment to collect adipose and other stem cells from patients in North America. They had already teamed up in the European market in January this year. The release explains that the North American agreement does not include Cytori’s Cellution System, which is designed to concentrate mesenchymal stem cells from material collected during liposuction, because it is under review by the FDA.
Cytori has heart disease trials underway in Europe and several more in other indications in Japan. Most applications are for cosmetic or reconstructive purposes.

Neostem has filed a patent for a “face lift” that injects fat and stem cells into a patient’s face. The procedure was developed by Vincent Giampapa, who runs the Giampapa Anti-Aging Clinic. We described this and other cosmetic procedures in a feature earlier this year called A superficial success.

CIRM announced its latest round of grants last week, and two companies were among the recipients. Among them, $5.4 million went to Novocell, which is working on diabetes, and $4.7 million went to BioTime, which is working on a way to expand human embryonic progenitor cells, which should be primed to differentiate but still capable of proliferating. (See preliminary work in Regenerative Medicine)
(You can get a list of all the recipients of the 15 early translational grants, totaling $67 million as a pdf.)

Posted by Monya Baker on May 08, 2009
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Our feature, A closer look at the single cell , profiles innovations in imaging from individual laboratories as well as commercial applications in gene expression.

I decided to commission it while reporting a story on cancer stem cells: researcher after researcher told me that the heterogeneity of cells within a tumour made it both essential, and impossible, to figure out what individual cells are doing. It does not include excellent genetic lineage experiments but rather focuses on studying cells in vitro.

Besides our feature, there’s a write-up of a recent conference bringing together scientists and industry.

Also, how did researchers get differentiated cells to beat when no one else had? Here’s our highlight of that Nature paper from Gladstone’s Benoit Bruneau.

And this highlight for researchers who want to start reprogramming human cells but lack the patience or expertise to pick the right colonies, check out this reprogramming tool published in Nature Methods by James Ellis of the University of Toronto.

Scroll below for a sneak peaks of three highlights.
A pair of papers in PNAS and Cell Stem Cell show ways to stabilize pluripotency and so make embryonic stem cells from non-permissive embryos. From MIT’s Rudolf Jaenisch and Scripp’s Phil Schultz

A Cell paper finds a microRNA for differentiation. It represses three major pluripotency genes and is repressed by one of them. From Ken Kosik of the University of California, Santa Barbara

A Nature Medicine paper finds early embryos have many more chromosomal abnormalities than anticiptated. What does that mean for embryonic stem cells? (This topic is covered for embryos in a News and Views)

Elsewhere in NPG this week:
Gene therapy researcher, James Wilson, warns stem-cell scientists not to repeat his field's mistakes
South Korea re-enters human stem-cell research
Neuroscientists claim growing pains with a commercial media
With OCT4, less is more : the first characterization of a post-translational regulation event occurring on OCT4 in a hES cell system
A panel of experts weigh in on a recent Nature Cell Biology that adult mice can generate new oocytes
A couple Nature Biotechnology papers compare the methylome in a variety of cells, including fibroblrasts, embryonic stem cells, and induced pluripotent stem cells. Read more

Here are peeks of the highlights that will go live next week.

Continue reading "Stem cells in NPG this week" »

Posted by Monya Baker on May 08, 2009
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The European Stem Cell Group is looking for new members. This group is funded by the EU Framework 7, and the goal is to set up some work groups to discuss prepublication work, figure out ways to analyze and manage data, and provide training. There will be an annual closed meeting. There are 20 spots available this year, and applications for associate principal investigators are due on May 29.

If you scan through the list of principal investigators, you will see some very familiar names. There are nine from the UK, 4 from Germany, 3 from the Netherlands, 2 each from France, Italy, Sweden, and Switzerland, and 1 from Austria.

Independent group leaders from EU and EEA countries with active stem cell research programs and recent publications are eligible to apply. Member information and application forms are available here. It’s a short form to fill out.

Speaking of Europe, the International Society of Stem Cell Research is having its annual meeting in Barcelona this July. You can learn about membership and the meeting here.

If you have an event to announce, you can email theniche[at]nature.com. We try to post upcoming meetings of interest on our events page.

Posted by Monya Baker on May 06, 2009
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Stem cell scientists in Ontario expect a boost from their province’s commitment to distribute an extra CAN$100 million for life science funding this year. Researchers in selected areas of life sciences need to state their intent to file by mid June, and submit final applications by August 31, with almost all the funds expected to be allocated by the end of the year.

In explaining the rationale for the program, Ontario's Minister of research and Innovation John Wilkinson specifically named the U.S. stimulus package and President Obama’s move to fund more stem-cell research.

“We are saying to Washington, and to the world -- we are willing to collaborate with you, but no
poaching of Ontario scientists allowed,” Wilkinson said, according to a statement released yesterday by the minister’s office.

Continue reading "Ontario scientists to get $100 million boost" »

Posted by Monya Baker on May 05, 2009
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Companies are starting to position themselves to deal with the complex patent situations around stem cells.

A stem-cell reagents company has joined forces with a young therapeutics company to create a third entity to share intellectual property around induced pluripotent stem cells. StemGent, which sells reagents and other products to differentiate and dedifferentiate stem cells, has joined forces with Fate, which is developing small-molecules that stimulate adults’ own stem cells. They have created Catalyst, which will provide services to biotech and pharmaceutical companies that want to use reprogramming technologies in drug development. I spoke with Fate Therapeutics CFO Scott Wolchko about the new entity, and the company is either unsure or isn’t saying exactly what Catalyst will do.

Continue reading "StemGent and Fate Therapeutics Form Latest iPS IP teams" »

Posted by Monya Baker on May 04, 2009
Categories: Intellectual property | Permalink | Comments (0) | TrackBacks (0)