The Niche

Consider this:
Mouse somatic cells were reprogrammed in 2006, 25 years after mouse embryonic stem cells were created.
Human somatic cells were reprogrammed in 2007, 9 years after human embryonic stem cells.
Rat somatic cells were actually reprogrammed a few weeks before rat embryonic stem cells were created.
(See Real rat embryonic stem cells )

Science declared reprogramming to be the breakthrough of the year and, while I’m certainly biased, it does make sense.

A subscribers-only review article by Doug Melton (whose in vivo reprogramming paper made a big splash this year) and John Gurdon (whose cloning of frogs in the 1960s anticipated current breakthroughs) chronicles the reprogramming field. They invoke the notion of “fleeting access” to explain why reprogramming rates are so low, particularly in specialized cells. The complexes of gene-inactivating proteins that cling to DNA sporadically dissociate from DNA allowing very short intervals during which reprogramming proteins can get to work. The concept explains why some cells are easier to reprogrma than others; most genes in embryonic cells and a subset of active genes in specialized cells will be more accessible. The actual reprogramming molecules differ depending on the technique (nuclear transfer into an oocyte, lineage switching, inducing pluripotency), but they conclude, however, the concept of fleeting access should appy in all cases.

In a news article describing reprogramming as the breakthrough of the year, Gretchen Vogel does a nice job surveying the year for non-specialists, but the format doesn’t let her list citations. (You can read Vogel's article for free if you register)

Here are some relevant (free) articles from Nature Reports Stem Cells. The first stems from the Melton paper which reprogrammed pancreatic cells in vivo.

Smash the (Cell) State!
A new quest for short cuts between specialized states could lay bare the machinery governing cell fate

Embryonic Stem Cells 2.0
Scientists' enthusiasm grows for induced pluripotent cells

Thomas Graf: Cellular identity and transdifferentiation

In the quest to switch one cell type to another, how far can tweaking transcription factors go?

Selected research highlights and meeting notes

Continue reading "A 2008 reprogramming round-up" »

Posted by Monya Baker on December 31, 2008
Categories: Reprogramming/Pluripotency | Permalink | Comments (0) | TrackBacks (0)

Why do I seem to be working harder and harder, but covering less and less? The vast majority of my readers, I’m sure, found the answer long before I did. In the eighteen months since Nature Reports Stem Cells has gone live, stem-cell happening have increased appreciably, inexorably, exhaustingly.

With so much content, we need filters more than ever, and on the cancer stem cell front, I just want to give a big thank-you to Alex Bersenev for his post over on Hematopoiesis, who summarized, organized, and emphasized important threads of my and others’ reporting on cancer stem cells. Another nice collection (including links to some open-access reviews) is on Jim Till’s cancer stem cell blog.

Also, and I meant to put this up long, long ago, his coverage of the ASH meeting focuses on aging and cancer. Check that out here.

Posted by Monya Baker on December 29, 2008
Categories: Blood stem cells, Cancer | Permalink | Comments (0) | TrackBacks (0)

Induced pluripotent stem cells derived from patients with the neurodegenerative disease called spinal muscular atrophy display characteristics of the disease, according to a paper published today in Nature. Thus, iPS cells look to be fulfilling their promise of being powerful tools to study sickness and screen for drugs to stop it. (See Reprogrammed skins cells are testing ground for new drugs ). iPS cells have been made from patients with a variety of diseases (See Ten diseases in a dish). However, this is the first demonstration I know of that shows that the cells show the phenotype of the disease.

Gut cancer tracked to stem cells
Two papers in Nature use an elegant reporter system to track down the cell that start cancer in the gut. See details below, or look for the research highlight next week.

Anti-wrinkle stem cells look ugly
Barely two weeks after the ISSCR released guidelines on the clinical use of stem cells, the Daily Telegraph reports that a Thai hospital that claims to cure wrinkles with injections of animal stem cells may instead put its patients into anaphylactic shock. (See also Stick to the guidelines and fewer get hurt and Offshore clinics need sensitive regulation )

Also noted: an account of Cytori’s fat-derived stem cells in a trial for heart disease from the San Diego Tribune. (See also Stem cells for the heart, a new wave of clinical trials)

And the stem cell deals for diabetes keep on coming. Just after Novocell sealed a collaboration with rock-star scientist Yamanaka, it snagged a deal with Pfizer, the world’s largest drug company.

Continue reading "Re-differentiated reprogrammed cells recapitulate patients’ disease; other breaking stories" »

Posted by Monya Baker on December 22, 2008
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Here’s a round-up of press releases and news articles of recent clinical trials in stem cells. Got something to add, email theniche[at]nature[dot]com

NerualStem has filed an IND to use its neural stem cell technology in a trial for Lou Gehrig’s disease.

StemCells, which already has a trial underway for Batten disease, just received FDA approval to start a trial for Pelizaeus-Merzbacher Disease (PMD), also a fatal brain disorder that affects mainly young children. The mechanism of the potential Batten disease therapy is to establish healthy neural cells that can help a patient’s own cells clear out some toxic garbage that builds up in the disease, the mechanism for PMD is to boost myelinization of neurons. (For work from a group that I think is unrelated, see Human cell transplants stop the shivers .) StemCells uses cells originally derived from fetal tissue.

Cytori has a 30-person clinical trial underway using fat stem cells for radiation induced injury.

Posted by Monya Baker on December 18, 2008
Categories: Clinical trials | Permalink | Comments (0) | TrackBacks (0)

It’s now official that the head of California’s stem cell institute will receive a salary of $150,000 for what’s considered a part-time job. Another post could garner $300,000; the state’s budget deficit has led the California governor to dismay at approving any government salaries not essential to the institute’s mission. (See Nature’s news story available for subscribers, plus previous blog posts.

Meanwhile, the Broad’s generosity continues, reports the Los Angeles Times. This time with a $25 million donation to the stem cell center at the University of California, San Francisco. (The link is not broken, you just have to scroll way down; also see the California Stem Cell Report.) The charitable foundation previously made similar gifts to the University of California and the University of Southern California.

Posted by Monya Baker on December 18, 2008
Categories: Funding and Resources | Permalink | Comments (0) | TrackBacks (0)

Nature recently published a paper by Sean Morrison and others finding that melanoma stem cells are not rare and that standard assays to identify tumorigenic cells fail to detect a large portion of them. This prompted two letters describing an earlier study by David Taussig and others which found that the antibodies used to detect the leukemogenic cells first identified by John Dick changed their behaviour. Another letter pointed out the role that the extracellular matrix plays in shielding transplanted cells from the immune response, and suggested that this could provide insight in developing immune-based therapies to cancer.

Here, we publish that correspondence along with replies from David Taussig, which describes evidence for that cancer stem cell hypothesis, including his own evidence that leukemia-initiating cells are less than 1 in 100 cells. Finally, a reply by John Dick and colleagues says that the effects described by Taussig do not apply to a key leukemogenic cell marker and goes on to describe misconceptions about the cancer stem cell model.

Read those letters below. Here are links to NPG's research and other articles on cancer stem cells.

Continue reading "Cancer stem cells: controversies and misconceptions" »

Posted by Monya Baker on December 18, 2008
Categories: Blood stem cells, Cancer | Permalink | Comments (0) | TrackBacks (1)

Blood-forming stem cells have recently garnered some attention. Genzyme’s drug to boost circulating stem cells in patients with blood cancers won FDA approval on Monday. Here is Genzyme’s description of its small molecule chemokine receptor antagonist. Also, two research teams from Stanford have found ways to make artificial versions of the microenvironments where blood forms (See below), and a third team from Germany and Switzerland describes away to track individual blood-forming stem cells .

But it's not all bloody. Esophageal stem cells made the cover of the Journal of Clinical investigation. The cells lining your throat strike an “exquisite equilibrium between proliferation and differentiation.” Researchers led by Anil Rustgi at the University of Pennsylvania, used DNA-labeling to identify a population of slow-cycling, apparently self-renewing cells in the esophagus. Then they studied these cells in three-dimensional culture and found that they grew into esophageal structures. When these cells were placed in immunodeficient mice, they formed epithelial structures, and when they were placed in a mouse model of esophageal reflux disease, they migrated to the site of injury. Here’s the press release.

Continue reading "Blood-forming and esophageal stem cells: find, see, manipulate" »

Posted by Monya Baker on December 16, 2008
Categories: Blood stem cells, Tissue-specific stem cells | Permalink | Comments (0) | TrackBacks (0)

The New York Times has a Q&A with Stanford’s Renee Reijo Pera, who “works at ground zero of the controversy over human embryonic stem cells.” It is a nice summary of relevant scientific questions, with a surprising take on Bush’s stem cell policy, plus a portrait of a scientist as a caring, curious individual.

The journal Stem Cells has also published a more technical series of interviews for the ten-year anniversary of human embryonic stem cell lines. Read interviews with Peter Andrews, Alan Trounson, and Rudolf Jaenisch
Also, see an interview with John Gearhart in Embo Reports.

Posted by Monya Baker on December 16, 2008
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Salaries and appointments for CIRM officials
After lots of people (including me) indulged in headlines touting half-million suppositions, the CIRM board decided to pay Bob Klein $150,000 a year for what it deemed a half-time position. The San Francisco Business Times provides a nice overview, including the potential hiring of California Democratic Party Chairman Art Torres for the vice-chair position at just over $300,000 per year, and Governor Schwarzenegger’s concerns about paying both these positions. The Sacramento Bee has an article on Torres.

Some companies get tools grants
In the last round of grants for creating new pluripotent stem cell lines, biotech companies cried foul that only applications from academics got the dough. (See What got funded.) They have less to complain about in this round. And while San Diego was bitterly disappointed that San Francisco (my fair city) won the seat of the California Institute of Regenerative Medicine, they should be cheered that four San Diego biotechs won grants. In addition, Duane Roth, one of the biggest “go-to” people in the San Diego biotech community, is reported to be Schwarzenegger’s pick for the vice-chair position eyed by Torres. XConomy reports that funds will soon be flowing to NovoCell for a pouch that can be used to transplant insulin-secreting cells without triggering an immune response, to Invitrogen (now known as the hard-to-Google “Life Technologies”) to use stem cells to model neurodegenerative disease, to Vala Sciences to make heart cells from stem cells, and to a joint effort by Fluidigm (which is in South San Francisco) and StemGent for techniques to find better ways to induce differentiated cells to pluripotency. The San Diego Tribune describes some funded technology more fully, along with the disappointments of one of the industry applicants that did not get funded. The two other companies to win grants were Gamma-Medica Ideas (with offices in Northridge, California, plus Norway and Canada) for ways to visualize single stem cells in the body and Vistagen (based in South San Francisco) for ways to use stem cells to screen drugs for potential liver toxicity.

Here is a list of the 23 grants awarded to 18 institutions, along with links to each application. Awarded funds totaled $19 million. This round of grants was targeted to develop technologies that could speed the development of therapies rather than become therapies themselves.

Posted by Monya Baker on December 12, 2008
Categories: Funding and Resources, Industry, Policy | Permalink | Comments (0) | TrackBacks (0)

One of the leading cell-therapy diabetes companies has just enlisted a rock star. The scientist who first described how to reprogram differentiated cells to pluripotency, Shinya Yamanaka of Kyoto University,has signed a deal with Novocell to use induced pluripotent stem (iPS) cells to replace the beta cells that are lost in diabetes.

Stem-cell approaches to diabetes continue to garner corporate interests. I described some stem cell diabetes deals involving NovoNordisk and Cellartis back in October.

Novocell and Geron are racing to develop protocols that can make beta cells from embryonic stem cells. The obvious experiment is to try these same protocols on iPS cells too. See our research highlight Perfect pancreatic cells, which links out to other stories.

Here’s the press release from NovoCell. Putting things mildly, it’s not big on details about financial or intellectual property agreements.

Yamanaka is famous for reprogramming cells to pluripotency, not nudging and coaxing and guiding pluripotent stem cells to glucose-responsive, insulin-secreting beta cells. No one is saying anything about what, exactly, Yamanaka might do to make iPS cells that are willing to be coaxed down this road. However, while I’ve yet to see anything in the peer-reviewed literature, more than one conference presentation has described that iPS cells created under different circumstances have different predilections for differentiation.

Also privately funded NovoCell itself is a bit of a new entity now. In November, CEO Alan Lewis announced that he’d be taking a job at the non-profit Juvenile Diabetes Research Foundation .

Posted by Monya Baker on December 10, 2008
Categories: Regenerative medicine | Permalink | Comments (0) | TrackBacks (0)

People who need a recent, accessible summary of what stem cells could do in medicine should check out this Newsweek piece, Will Stem Cells Finally Deliver? by Harvard professors David Scadden and Anthony L. Komaroff.

For those who want more-technical reading, Science has pulled together a special issue on organ development, that includes articles on regeneration of pancreas and liver cells (Marcus Grompe and Ken Zaret), stem cells’ origin in organogenesis (J.M.W. Slack), cardiogenesis (Ken Chien, Ibrahim Domian, Kit Parker), and more.

And, I’d be remiss not to mention the special issue that Nature put together several months ago on regenerative medicine. Here’s a web focus of reviews and relevant research articles, as well as accessible, informal interviews with experts including Robert Boyd, Ken Chien, Sheng Ding, Geoff Gurtner, Christine Mummery, and Len Zon.

Posted by Monya Baker on December 08, 2008
Categories: Regenerative medicine | Permalink | Comments (0) | TrackBacks (0)

The New York Times has a story out today about highlighting a study that shows that couples who have embryos in storage generally don’t want them to become someone else’s children.

Last year, the lead researcher of this work, published results in Science that surveyed couples who were undergoing fertility treatments and found that 49% of over 1000 couples with stored embryos said they would donate embryos for medical research. Interestingly 60% were willing if a purpose of research, like making stem cells, was given. (See Survey: US couples willing to donate embryos) The lastest publication is in Fertility and Sterility and is summarized in a press release from Duke.

Meanwhile, Geoff Lomax at CIRM told me the Institute is working out a mechanism to figure out if various embryonic stem cell lines as well as induced pluripotent stem cell lines have been acceptably derived. In short, officials there are preparing a very, very carefully thought out registration form about how a line was derived so that CIRM (and presumably other states) can decide that it can be used in research. There are check boxes for whether and how informed consent was obtained for gametes, embryos, and tissue, as well as whether donors received any sort of payment. The goal of a single, simple form is to take some of the paperwork and guesswork out of deciding what lines researchers can use in experiments. (Lomax said he’s happy to read suggestions sent to Glomax[at]cirm.ca.gov; please send them in by Friday, December 12th; this Fri.)

A related discussion(free after registration) is underway in response to an article by University of Wisconsin-Madison bioethicist Robert Streiffer, which made headlines (subscription) for his analysis that some lines on the NIH Stem Cell Registry (those that the President declared eligible for federal funding) were obtained without informed consent.
This kind of work Lomax is doing reminds me of what Streiffer told me when I interviewed him months ago: it’s not just science that advances in response to experience, so do standards of informed consent. (See When the past catches up with the present for reaction to worries that the NIH did not properly evaluate informed consent.)

Posted by Monya Baker on December 05, 2008
Categories: Ethics | Permalink | Comments (0) | TrackBacks (0)

CIRM added yet another country to its list of collaborators, Spain, on December 3rd.
That’s the fifth country this year. The others are
Japan (Nov 18)
UK (Oct 20)
The Australian state, Victoria (June 18) and
Canada (June 18)

I went to the signing ceremony of the UK collaboration, where race-card-driver-turned-executive-turned-British-official Paul Drayson met with CIRM head Bob Klein to sign the three-page memorandum of understanding. They let me read it. It wasn't very specific.. Patent laws for each country would still apply, for instance. Though researchers will still apply for grants from their respective geographic locales, they will formally be able to name collaborators far, far away.

In other news, the chair of CIRM’s governing board, Robert Klein, may be seeking a salary of $508,750, according to the California Stem Cell Report. (See posts on Dec 1 and Dec 4). The folks over on King Street seem to be doing well, according to their salary schedule. Just before CIRM president Alan Trounson was hired at just under a half million dollars a year, I wrote an article chronicling the Institute’s search for a president and trolled through tax filing to find salaries of the scientific heads of several grant-giving agencies. (See that here, but note that the figures are a bit old.)

Posted by Monya Baker on December 05, 2008
Categories: Funding and Resources, Policy | Permalink | Comments (0) | TrackBacks (0)

Geron is unhappy that the European Patent Office has rejected claims of patents it has licensed from the Wisconsin Alumni Research Foundation. The argument as I understand it is that the European Patent Office followed rules forbidding patents on inventions that involve the destruction of embryos. Geron argued that nowadays researchers don’t have to destroy embryos because they can get embryonic stem cell lines from a cell bank, but the EPO didn’t buy that. (But you can read the arguments for yourself at the EPO.) For Geron’s side, see the press release . WARF’s press release emphasized that the decision was based on laws peculiar to Europe and had no bearing in the US.

Despite opposition from many scientists and activists, WARF’s claims over embryonic stem cells were upheld earlier this year. The first two in March, (See Nature news story) and the third in June.(See WARF press release.
(See also A perfect storm in patents )

Posted by Monya Baker on December 05, 2008
Categories: Intellectual property | Permalink | Comments (0) | TrackBacks (0)

A study in Cell Stem Cell finds that web sites that offer stem cell treatments over the Internet make lots of bogus claims, and the leading organization of stem cell scientists has issued a patient handbook of questions to ask potential providers, plus guidelines for the clinical translation of stem cells.

We have an excellent commentary that explores the issue from the view of various stakeholders including patients, providers, regulators, and scientists. It’s written by Doug Sipp of RIKEN in Japan and Sorapop Kiatpongsan of Harvard and Thailand’s Chulalongkorn University. Here is the NatureNews story.

This feature charts dilemmas faced by practitioners and patient advocates.
Stem cell researchers face down stem cell tourism

This news story includes opinions from diverse members of the task force and others in the community.
Stem cell society condemns unproven treatments

Links to a story in the popular press and a draft of a news story is below.

Continue reading "Stopping snake-oil stem cell treatments" »

Posted by Monya Baker on December 03, 2008
Categories: Ethics, Policy | Permalink | Comments (0) | TrackBacks (0)

Given the excitement generated bythe recent Nature Paper, here's a list of cancer stem cell articles published by Nature Reports Stem Cells.
Also check out Nature's web focus on cancer stem cells.

Cancer stem cells, becoming common
Tumour cells that can initiate a new tumour are not so rare as previously thought, putting the concept of the 'cancer stem cell' under the spotlight again.
Published online: 03 December 2008; doi:10.1038/stemcells.2008.153
Full Text

Two of a kind
Cancer stem cells use an embryonic stem cell-like transcriptional program to induce and maintain tumours
Published online: 11 September 2008; doi:10.1038/stemcells.2008.126
Full Text

Stem cell meeting 2008: in with the old, in with the new
Although excitement around advances in reprogramming somatic cells shows no signs of abating, new ideas regarding the field are surfacing.
Published online: 17 July 2008; doi:10.1038/stemcells.2008.108
Full Text

A mutant Methuselah for blood-making progenitors
Cells that regenerate blood increase tenfold in mutant mice
Published online: 24 April 2008; doi:10.1038/stemcells.2008.73
Full Text

Cancer and embryonic stem cells share genetic fingerprints
At least two modules of genes promote stemness
Published online: 17 April 2008; doi:10.1038/stemcells.2008.62
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Skin cancer needs beta-catenin
Without beta-catenin cancer stem cells no longer support tumours
Published online: 03 April 2008; doi:10.1038/stemcells.2008.57
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Cancer and stem cells: Beckman conference
Cancer cells emerge when checkpoints fail
Published online: 13 March 2008; doi:10.1038/stemcells.2008.47
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Stuck on youth
Some cancer stem cells retain an embryonic pathway
Published online: 24 January 2008; doi:10.1038/stemcells.2008.23
Full Text

MicroRNA reins in tumor-initiating cells
A microRNA that silences two oncogenes is quiet in cancer stem cells
Published online: 03 January 2008; doi:10.1038/stemcells.2007.137
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Leukemia might elbow out blood makers
A new mouse model helps researchers study human cancer cells
Published online: 01 November 2007; doi:10.1038/stemcells.2007.112
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Cancer stem cell sightings and slightings
Experts debate the rarity and relevance of 'tumour-initiating cells'
Published online: 27 September 2007; doi:10.1038/stemcells.2007.93
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Stem cells not all to blame
Cells driving tumor growth may not be all that rare
Published online: 16 August 2007; doi:10.1038/stemcells.2007.75
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Stem cell meeting 2007: Routes and roadblocks on the way to cures
While the basic side of stem cell research is prospering, several talks on translating research to therapy were sobering reminders of the challenges ahead.
Published online: 12 July 2007; doi:10.1038/stemcells.2007.52
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What's the relationship between stem cells and tumors?
Like some stem cells, cancer cells can grow without pause. Some cancers use stem cells' tricks to do this, and so some cancer researchers study stem cells.
Published online: 14 June 2007; doi:10.1038/stemcells.2007.25
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The space race
Defective stem cells physically compete for space in the niche of the Drosophila ovary
Published online: 24 January 2008; doi:10.1038/stemcells.2008.24
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More reprogramming tips
A gene used to reprogram differentiated cells blocks microRNA processing
Published online: 06 March 2008; doi:10.1038/stemcells.2008.43
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Pituitary stem cells found using a general stem cell marker
Genetic approaches identify a distinct, postnatal stem cell population
Published online: 15 May 2008; doi:10.1038/stemcells.2008.77
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What comes after iPS?
Though applications of reprogrammed cells will be valuable, the questions they engender will be just as important
Published online: 03 April 2008; doi:10.1038/stemcells.2008.54
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Posted by Monya Baker on December 03, 2008
Categories: Cancer | Permalink | Comments (0) | TrackBacks (0)