Stem cell research highlights 2010

For the final post of 2010, here are some stem cell highlights from the past year (in no particular order).

• Three trials based on embryonic stem cells were approved by the FDA: two for forms of vision loss (Stargardt's and macular degeneration) and one for spinal cord injury. (Update on 1/3/11: only two trials received FDA approval in 2010. The macular degeneration trial received approval today.)
• The man who has come to be known as the Berlin patient is shown to be free of HIV infection after a bone marrow transplant from a donor with a mutation that produces an immune system that is resistant to the virus (our blog entry). This mutation is the basis for two CIRM disease teams: one at UCLA and one at City of Hope.
• A federal judge temporarily halted federal funding for human embryonic stem cell research. Funding was quickly restored but the final ruling in the case is still unknown (our blog entry). (I guess this one is more of a lowlight that a highlight.)
• Two groups showed that adult cells can be reprogrammed to a different cell type without first passing through an embryonic-like state. CIRM grantee Deepak Srivastava, who directly converted mouse fibroblasts into heart muscle cells, thinks this discovery could one day lead to drugs that directly convert tissue types within the body.
• The first functioning organ — in this case a miniscule liver — was grown from embryonic stem cells (our blog entry).
• Five of the CIRM-funded Major Facilities opened their doors (UC Davis, UC, Irvine, USC, Stanford, and UCLA). The $271 million provided by CIRM leveraged more than 800 million in private and institutional funding. The construction of those buildings has been estimated to create 13,000 job years of employment and $100 million in tax revenue for the state.
• A Harris Interactive/Healthday poll found widespread support for embryonic stem cell research, with 73% saying that the research should be allowed.
• Two CIRM grantees were honored with major awards. Joanna Wysocka of Stanford University was awarded the Outstanding Young Investigator Award from the International Society for Stem Cell Research and Shinya Yamanaka of Kyoto University and the Gladstone Institute for Cardiovascular Disease/UCSF won the prestigious Kyoto Prize for Advanced Technology.
• Derrick Rossi of Harvard University developed a new way of reprogramming adult cells into embryonic-like iPS cells (our blog entry). The technique avoids the use of integrating virus and is significantly more efficient than previous methods.
• Costa Rica shut down an unregulated stem cell tourism clinic to protect patients from expensive unproven procedures (our blog entry). Aware of the growing risk of stem cell tourism, the ISSCR unveiled a new web site to help people who are considering traveling to receive stem cell therapies. 

Feel free to add your own highlights.

We'll be back for an action-packed 2011!

A.A.

Stem cell therapies for diabetes: wrap them up

A pancreatic beta cell.
Image by Itkin-Ansari lab

Type 1 diabetes has been a major focus of CIRM funding, including a disease team award to San Diego-based ViaCyte that is expected to bring a therapy to trial within four years.

Sanford-Burnham has a great post on their blog about how stem cell therapies for diabetes might work. They discuss the work of Pamela Itkin-Ansari, who is working with ViaCyte to develop a way of wrapping transplanted cells to protect them from the immune system. They write:

Her laboratory has placed human pancreatic precursor cells in an immuno-protective device and transplanted them into mice. She was testing whether precursor cells will mature into productive beta cells in the body and whether the encapsulation device, made from a material akin to Gore-Tex, could prevent the immune system from attacking transplanted cells.

Early studies have been positive, they write.

“We were excited to see how well they did,” says Dr Itkin-Ansari. “We could see evidence of new beta cells forming and replicating. That meant the environment in the device was conducive to beta cell maturation and function. We wondered whether  T cells, although unable to penetrate the device, would cluster around it. Interestingly, we found no evidence of an active immune response, suggesting that the cells in the device were invisible to the immune system.”

A.A.

Genetic regions guide embryonic stem cell development

Joanna Wysocka

Stem cell research generally doesn’t make the news unless it’s a story about diseases and cures. We push toward cures every day here at CIRM, but we also fund a lot of the less flashy science that — though it doesn’t make the daily news — we think will one day underlie many of those future cures.

A recent paper by CIRM grantee Joanna Wysocka at Stanford is one of those that sounds pretty basic but could end up as an important milestone in understanding how human embryonic stem cells form the various types of tissues in the body.

Wysocka, who was last year’s Outstanding Young Investigator at the International Society for Stem Cell Research meeting, found thousands of DNA regions, called enhancers, that control the activity of far distant genes. Of the enhancers they found, more than two thousand carried molecular tags that held the genes in a state much like swimmers at the start of a race — ready to spring to action but also held in check. As the stem cells matured into a given cell type, those tags holding the enhancers in check fell away and the gene was able to spring off the starting block.

In a Stanford press release Wysocka said:

“This is going to be an enormous resource for researchers interested in tracking cells involved in early human development. It will be very interesting to learn how these enhancers affect gene expression in each cell type.”

Having found these enhancers scientists can develop better tools for maturing embryonic stem cells or iPS cells into the desired cell type — heart cells, pancreas, skin, nerves or anything else. Right now, coaxing stem cells to become the desired cell type is a big hurdle and is not terribly efficient for some cell types. Anything that improves that process is a step toward those flashier papers about stem cells and cures.

CIRM Funding: Joanna Wysocka (RN1-00579-1)
Nature, December 15, 2010

A.A.

More on the Berlin patient, stem cells, and a cure for HIV

The response to the story about the Berlin patient who was reported cured of  HIV has been incredible, but in this case it’s also a little troubling. What I see in comments on news stories or in tweets is that we have an uphill battle in terms of educating people about stem cells.

The stem cells used to eliminate this man’s HIV infection were from the bone marrow. Essentially, what he got was just a really great bone marrow transplant, because the transplanted cells were resistant to HIV. The bone marrow houses the blood-forming stem cells that create the entire blood system. Those blood-forming stem cells were the first stem cells to be identified, back in 1998 by Stanford’s Irv Weissman.

CIRM’s two disease teams are working on even more sophisticated -- and safer -- bone marrow transplants that could bring this same cure to thousands of people who need it. (Summaries of those teams are available here and here.)

What concerns me is that many of the comments on news stories or Tweets are tying this HIV therapy to embryonic stem cells or even abortion. Just so we’re clear here, an aborted fetus has no embryonic stem cells. None. Human embryonic stem cells come from IVF embryos left over after a couple completes their family. (Paul Knoepfler of UC Davis has a good description of how those human embryonic stem cell lines are created.) These embryonic stem cells are amazing — they can form any tissue in the body, which can become cures or unlock the mysteries of how diseases form.

In the case on the Berlin patient, it was adult, blood-forming stem cells that were the basis of the cure. For other diseases, the cure may come from embryonic or reprogrammed iPS cells. At this point, we don’t know which cell type will cure which disease. All we know is that we need cures, and like the Chilean miners who dug three rescue holes to have one succeed, we’re working all angles in order to be successful in our quest for cures.

A.A.

Stem cell therapy treats HIV, basis for two CIRM disease teams

There’s a lot of buzz today over a paper in the journal Blood declaring a man who has come to be known as the “Berlin patient” cured of HIV.

The same patient was featured in the New England Journal of Medicine in February 2009. A man infected with HIV needed a bone marrow transplant for his leukemia. The doctors gave him the transplant from a person who was naturally resistant to HIV infection. The donor’s bone marrow cells contained a mutated protein called CCR5, which is required for HIV to enter the cell. This follow-up work presents the results of numerous tests that failed to find evidence of remaining HIV infection.

In the paper, the authors write: "In conclusion, our results strongly suggest that cure of HIV has been achieved in this patient."

This story discusses an interview in a German publication in which the Berlin patient discusses the difficulties he faced during the course of the treatment. Although I don’t read German, the English summary of that interview makes it clear that bone marrow transplant is not an easy answer, and that making the transplantation more tolerable needs to be part of a future therapy.

The Berlin patient is the basis for two different CIRM disease teams. Although the therapy was a success, there aren’t enough donors who lack CCR5 to provide bone marrow for all people with HIV infection. Instead, the CIRM groups are removing the patient’s own bone marrow and attempting two different approaches at manipulating those cells to remove CCR5 function. They will then give the modified bone marrow back to the patients, hopefully providing a life-long resistance to HIV infection.

Here are summaries of the CIRM disease team awards at City of Hope and UCLA. We also have a video about the technique, featuring the lead researcher at City of Hope and HIV/AIDS advocate Jeff Sheehy, who serves on the CIRM governing board.



A.A.

CIRM looking for a few good ambassadors

On Wednesday the CIRM governing board heard from the external review panel that evaluated CIRM’s activities. (You can read their report and bios here.)

One especially interesting portion of the conversation had to do with outreach: how do we let the people of California know about our progress? The panel and several board members mentioned our video program (YouTube videos are available here) and social media (here’s our Twitter and Facebook pages, if you want to follow us).

Beyond these attempts at reaching the people of California, the panel recommended engaging patient advocates and building communities of stem cell evangelists who can talk about the power of the research in California.

I’d love feedback. Anyone reading this blog is at least somewhat engaged with CIRM and stem cell research. Would you be willing to help us spread the word? Do you have recommendations for how we can reach more people? Are you a patient advocate who would like to get more involved in rallying support for CIRM and stem cell research?

If yes, let me know your thoughts on what we can do at CIRM or how you want to help.

Just keep in mind that although we have quite a bit of money for research, we can only spend a tiny fraction of that for administration and our staff is small.

I look forward to your ideas!

A.A.

California funds the most stem cell research not eligible for federal funding

Aaron Levine from Georgia Tech published a letter in Nature Biotechnology assessing state funding for stem cell research, and he came to a conclusion that matches our own. In a press release he said:

"There's no question that these state programs drew a lot of scientists into the field."

That’s good news; Given the difficulty of generating new cures, we need as many scientists as possible invested in the search. Bringing in these new scientists was a major focus of CIRM’s early awards, including the Training and SEED awards, and the New Faculty awards that help young faculty build stem cell research programs in their labs.

The paper analyzed stem cell research funding by California, Connecticut, Illinois, Maryland, New Jersey and New York. In the paper the team wrote:

Although the state stem cell programs differ, they each share at least two goals: advancing promising science, including research not eligible for federal funding during the Bush Administration, and returning economic benefits to their state.

Of the six states, California and Connecticut fund the highest percentage of human embryonic stem cell research, and California funds the highest percentage of research that would not have been eligible for federal funding. The grants are primarily ones focused on deriving new embryonic stem cell lines, which cannot be federally funded.

The group posted their data online: http://www.stemcellstates.net/index.php

This paper didn’t analyze the economic return based on state funding, but if it did it would have found that CIRM’s building projects are estimated to have generated 13,000 job-years of employment, bringing in $100 million in tax revenue.

I spoke with Levine recently, who commented on CIRM’s searchable list of funded awards. That table was (and continues to be) a labor of love for me, so it was nice to hear that it was useful.

A.A.

CIRM grantees at UCI collaborate on Swiss spinal cord injury trial

More good news for people with spinal cord injury out of the University of California, Irvine: two CIRM grantees collaborated with Palo Alto-based StemCells Inc. to develop a neural stem cell therapy that has been approved for a trial in Switzerland.

Brian Cummings and Aileen Anderson did the preclinical work on the possible treatment, which will be tested in people with chronic spinal cord injury. Their colleague at UCI Hans Keirstead did the preclinical work on a possible embryonic stem cell treatment for acute injury, which Geron is now testing in a clinical trial.

A press release from UCI discusses the team's approach:

Their efforts have shown how these cells, when transplanted into damaged spinal columns, can differentiate into neural tissue cells — such as oligodendrocytes and early neurons — and migrate to injury sites. In recent studies, the researchers found that the treatment restored hind-limb function in mice when transplanted in the early chronic period after spinal cord injury.

CIRM funds research in spinal cord injury that includes embryonic, iPS and adult stem cells with the idea that we won't know which approach works best until we see the clincal trial results. You can see a list of funded spinal cord injury awards.

The work that led to this clinical trial took place before CIRM funding became available. CIRM is now funding follow-up research by Cummings and Anderson that could lead to advances on the Swiss trial.

Oswald Steward, who directs the Reeve-Irvine Research Center where Anderson, Cummings and Keirstead all conduct research and is a member of the CIRM governing board helped create this video about stem cell therapies for spinal cord injury. Thanks also to Roman Reed, who talks about living with spinal cord injury.

Oral arguments made in federal stem cell case

Yesterday a three judge panel of the U.S. Appeals Court heard oral arguments in the legal case that has threatened federal funding for human embryonic stem cell research since August.

Nature has an excellent piece with excerpts from the arguments. The central issue is whether funding for research using human embryonic stem cells is in violation of the Dickey-Wicker amendment, which prohibits federal funding the destruction of embryos. The NIH had read that amendment to mean that they can't fund the creation of new stem cell lines, which does destroy the embryo, but they can fund research using the lines created with private funding. The plaintiffs have argued that the very use of those cells encourages the destruction of embryos and thus violates the law.

This seems like a good time to point out that the leftover IVF embryos used to created human embryonic stem cell lines were donated by people who would otherwise have discarded the embryos without donation. Adoption is an alternative, but not one that is commonly chosen.

But I digress. Here's a particularly interesting excerpt from the Nature story (Thomas Hungar argued for the plaintiffs):

Hungar: Federal funding of this research to the tune of hundreds of millions of dollars absolutely creates more than a minimal risk that an embryo is going to be destroyed.

Judge Ginsburg: [The Dickey-Wicker amendment] says in which [an embryo is destroyed], not for which [an embryo is destroyed.]

Hungar: The fact that this is federally funded research creates an incentive [for that destruction.]

Ginsburg: So you’re back to the incentive argument again….This is all one argument: the research is a continuum….It started with the destruction [and derivation of the cell line and goes forward open-endedly after that]….and [your] reason for reading it that way is the incentive…..There’s research into making lab equipment and there’s research using [that] equipment. [There’s no reason to say they’re the same.]….This is pretty straightforward [He reads from the statute:] `research in which human embryos are destroyed, not were destroyed.’

It isn't clear how long the court will take to rule in this case.

This trial only relates to federal funding. CIRM funds the creation of new cell lines and research using those lines. You can see a list of all CIRM awards that have the goal of creating new human embryonic stem cell lines on our searchable grants page.

Run down on CIRM's quest for the next chair

The purpose of this blog is to talk about the advances in stem cell science, and the progress being made by CIRM grantees. However, sometimes CIRM itself is a focus of  news that warrants us updating readers about our own activities.

There has been much speculation in the news about the person who will become the new chair of the agency's 29-member governing board. Our current chair, Robert Klein, was elected to a six-year term on December 17, 2004. On December 15, the governing board will vote on the person who will hold the next term.

We’ve posted a statement on our website about that process, including our answer to the most common question about who nominates candidates:

A: Under Proposition 71, four Constitutional Officers (the Governor, the Lieutenant Governor, the Treasurer and the Controller) are responsible for nominating candidates for Chair and Vice Chair of CIRM’s Governing Board, which is composed of 29 members (27 members appointed by the constitutional officers, the Speaker of the Assembly and the Senate President Pro Tem, in addition to the Chair and Vice Chair.) The Governing Board elects a Chair and a Vice Chair from among the nominees.

As of posting, here is the run-down of nominations:

• Governor - Chair: Robert Klein
• Lieutenant Governor - Chair: Robert Klein
• Treasurer - Vice-Chair: Art Torres
• Controller - Chair: Art Torres; Vice-Chair: Jeff Sheehy

Stay tuned for the December 15 vote. We’ll issue a press release as soon as that happens, and will be posting to our twitter feed (CIRMnews) and Facebook page (http://www.facebook.com/CaliforniaInstituteForRegenerativeMedicine). You will also be able to listen in to that meeting live. When the agenda is posted to our list of upcoming meetings it will include a URL for that audio webcast.

Here’s some more information about our current board members.

A.A.

Protein Linked to Normal Prostate Stem Cells and to Cancer

When I was the editor of a national magazine for physicians, I told my writers to do any story they found on prostate issues, with our overwhelming male audience then, I knew those stories would get high readership scores. My readers back then would have loved today’s news out of UCLA. The team there, led by CIRM grantee Owen Witte, found that the inhibition of a certain protein slowed the growth of an aggressive form of prostate cancer in animal models.

Scientifically, though the immediate excitement is over the double life this protein leads normally in the prostate. It regulates self-renewal of normal prostate stem cells needed to repair any injured cells. But it also aids the transformation of healthy cells into prostate cancer cells. The protein, called Bmi-1, has been associated with higher grade cancers and is predictive of poor prognosis. A UCLA press release quotes Witte as saying:

“We conclude by these results that Bmi-1 is a crucial regulator of self-renewal in adult prostate cells and plays important roles in prostate cancer initiation and progression. It was encouraging to see that inhibiting this protein slows the growth of even a very aggressive prostate cancer, because that could give us new ways to attack this disease.”

You can view a video about attempts to attack cancer stem cells here:



Cell Stem Cell, December 3, 2010
CIRM funding: Rita U. Lukacs (T1-00005, TG2-01169)

D.G.

HIV/AIDS video for World AIDS Day

World AIDS Day seems like a good time to revisit a video we made this year featuring CIRM board member Jeff Sheehy, who is a long-time advocate for HIV/AIDS research:



CIRM is funding two teams of researchers working on different approaches to treating HIV/AIDS (one at UCLA and one at City of Hope). Both involve replacing a person’s blood-forming system with cells that are resistant to infection.

For more background on the work, you can watch a Spotlight on HIV/AIDS by one of the disease team leaders, John Zaia of City of Hope.

All of these resources are available on our HIV/AIDS disease page, along with information about the grants we fund that target HIV/AIDS.

Here's hoping that on this day next year we'll be able to talk about progress being made by the two outstanding teams of researchers working to cure this devastating disease.

A.A.

ACT files to test embryonic stem cell-based therapy for macular degeneration

Advanced Cell Technology has filed an application with the FDA to begin an early phase trial of an embryonic stem cell-based therapy for macular degeneration. If the company name sounds familiar, that’s because it’s the same company that on November 22 received FDA approval to begin a trial for Stargardt’s macular degeneration. Both trials are testing the same cells. In a press release, the company said:

Company scientists view the use of the same hESC derived RPE cells for both trials as the most efficacious approach, as it permits the Company to leverage its experience with the FDA that it gained through the process of obtaining approval for the Stargardt’s clinical trial to expedite the approval of its clinical trial in Dry AMD.

As with the company’s Stargardt’s trial and Geron’s spinal cord injury trial, this new trial will be assessing safety in a very small number of patients — standard practice for any new therapy being tested. After proving safety in a phase I trial, a larger trial will assess whether or not the potential therapy is effective.

It’s exciting to see embryonic stem cell derived therapies reaching patients. In general, more trials fail than succeed and we don’t know in advance which ones are going to work. That’s why there are hundreds of cancer trials going on around the country, and why we need hundreds of stem cell trials too. Hopefully CIRM’s macular degeneration disease team led by Mark Humayun at USC won’t be far behind ACT with their own version of an embryonic stem cell-based therapy for macular degeneration. And hopefully, one of them will provide a cure for the roughly 30 million people worldwide who are losing or have lost vision due to the disease.

Here’s a video about the CIRM disease team project:



A.A.

A stem cell by any name

This past year has brought a number of advances in creating reprogrammed iPS cells and in directly reprogramming mature cells into a different cell type. With each advance comes the question: Where does this leave embryonic stem cells? And each time, stem cell scientists remind us that the advances are great and could potentially lead to exciting therapies, but there’s a lot to learn in terms of safety.

An AP story today has a great quote from George Daley of Children's Hospital Boston and the Harvard Stem Cell Institute, whose lab has been responsible for many of those advances:

When we make a duck look like a cat, it may look like a cat and meow, but whether it still has feathers is an issue.

It was a good weekend for analogy. CIRM grantee Paul Knoepfler at UC Davis came up with this one on his blog:

If ES cells are like a safety and road tested Ford (a model that's been around a dozen years), then IPS cells are a shiny new sports car that even the experts know very little about. We are not sure how its accelerator or brakes work. It hasn't been crash tested. It looks really fast and everyone thinks it has a lot of potential, but it's only been around a very short time.

If you had to get you and your loved ones safely from point A to point B, which kind of car would you go in at this time?

IPS cells have outstanding potential, but they are still somewhat of a mystery, particularly in terms of their safety. I predict that in a few years, there will be safe iPS cells, but we aren't there yet. We just don't know enough.

A comment on Knoepfler’s blog points out:

I would say that adult stem cells are cadillacs: been around a long time, you know what you are getting, solid

Depending on which analogy you prefer, CIRM funds either an entire zoo, or a full parking lot. Here’s my own analogy: Some diseases are more like mountain passes and require a sure-footed SUV. Others are winding highways ideal for racing. CIRM grantees are test-driving all types of stem cells with the goal of learning which provides the best transportation to a cure for different diseases. If all we have are Cadillacs we’ll have a hard time with diseases that require a space-saving Smart car.

You can filter our list of all funded stem cell research awards according to the stem cell type being used.

A.A.

Sherley vs. Sebelius and the redefinition of "research"

The Sherley vs. Sebilius case that has put human embryonic stem cell research on pause throughout the country has an interesting new twist. According to ScienceInsider the Boston Biomedical Research Institute, which employs James Sherley, one of the two scientists who sued to block federal funding for human embryonic stem cell research, has joined the pro stem cell side. They filed a motion explaining the many ways BBRI researchers intend to use human embryonic stem cells in the future.

That case is due to be heard December 6 and has a number of key scientific leaders in addition to the BBRI weighing in on the side of the NIH. The University of Wisconsin filed an amicus brief, which both the Genetics Policy Institute and the Coalition for the Advancement of Medical Research asked to join.

There’s one interesting aspect to the case that hasn’t received much attention. It came up in an amicus brief filed by the regents of the University of California. The brief, which is remarkably entertaining reading (no really), makes the point that the case would fundamentally redefine what is meant by a piece of “research.” The logic goes like this:

• The plaintiffs argue that the Dickey-Wicker Amendment prohibits the destruction of human embryos (so far so good).
• And that deriving new human embryonic stem cell lines from IVF embryos does, in fact, destroy the embryo (still good — this is why the NIH can’t fund the creation of new lines)
• And that since human embryonic stem cell research requires using stem cell lines that once resulted in the destruction of an embryo, that work also can’t be funded by the NIH (huh?)
• So, a piece of a research in a proposal to the NIH includes not only the proposed work, but everything that came before it.

The UC Regents brief had this to say:

If an activity is included within the proposed project and is funded by the NIH grant, then, by definition, that activity is part of the funded research. If the activity is not included in the request for funds, no NIH funds are made available for that activity, no NIH grant funds are used for that activity, and, by definition, the activity is not part of the funded project. Thus, if grantees do not request funds for the derivation of hESCs or the creation of hESC lines and NIH does not award funds for those activities, by definition, NIH has not funded any research in which embryonic stem cells are derived or propagated.

(Emphasis added)

So, by the logic of the plaintiffs, if a researcher proposes carrying out research with iPS cells that follows up on knowledge gained from work with embryonic stem cells, is that iPS work also the indirect result of a destroyed embryo and therefore not fundable by the NIH?

It doesn’t make a lot of sense.

A.A.

Vision loss trial based on embryonic stem cells begins

The FDA has given the green light to the second trial based on embryonic stem cells — this one for a genetic form of blindness called Stargardt’s Macular Degeneration. The treatment, developed by Advanced Cell Technology, involves replacing the the layer of the retina damaged by the disease, called the retinal pigment epithelium, with new RPE cells derived from embryonic stem cells.

This approach is similar to one under development by a CIRM macular degeneration disease team led by Mark Humayun at the University of Southern California.

Nature wrote about the ACT trial:

In the trial, 12 individuals at several US medical centres will receive injections of the cells directly into the eye to test the safety of the procedure. (Although the disease begins to take its toll at around 6 years of age, the trial will start with patients who are over 18.)

The small size of the trial is typical for a Phase I/II trial, which is primarily looking to ensure that the technique is safe before testing it in more people. Nature went on to quote ACT’s chief scientific officer Robert Lanza:

The advantage, of course, is that we’re talking about a very small number of cells going into a very local area,” he says. Using instruments that can track a single retinal cell in the eye in real time, the researchers will also be able to easily monitor patients’ progress.

“Also, with the eyes there are very objective tests for visual acuity,” he notes, “so we can measure performance gains very objectively.” Tracking improvement after spinal cord injury, on the other hand, is notoriously tricky.

This video features Mark Humayun discussing his macular degeneration work:




A.A.

Rock stars of science: making science cool

There’s been a lot of discussion recently about explaining science to the public, capped by GQ photo shoot featuring scientists and rock stars as part of the Rock Stars of Science campaign. I was happy to see our own Catriona Jamieson of UCSD featured with British singer-songwriter and rapper Jay Sean.

According to a story in The Scientist:

Since the campaign was launched, nearly 250,000 people have visited the Rock Stars of Science website. Videos of the Rock Stars Hill briefing on September 24, 2009 were seen by more than 4,500 people, according to Research!America. And the events have attracted media attention. For example, ABC gathered some scientists from the 2009 Rock Star campaign in a panel on Alzheimer's on Nightline.

A few big name scientists seem impressed:

Anthony Fauci, director of the National Institute of Allergies and Infectious Diseases and 2009 Rock Star Scientist, said he's gotten feedback that suggests the campaign helps encourage young people to contemplate careers in science. "The message was that you can get the same thrill and rush from science as you can from being a rock star," he said, "so from my point of view it was a home run." Collins, another rock star alum, said in an email he thinks the campaign is a "terrific" vehicle to excite kids. "The effort aims to show scientists as a very cool part of our culture," he said. "Kids need to know that you don't have to be a total geek to be a great scientist."

At the same time, Nature recently ran a piece giving scientists some how-tos when it comes to talking about their work. Because it doesn’t do any good to be a rock star of science if you can’t effectively explain what your scientific progress to the public, to law-makers and to science skeptics. The Scientist describes the much-feared Sagan effect that might be preventing scientists from communicating more passionately about their work:

Some worry that media interaction can taint careers. The 'Sagan effect', named after the astronomer and famous science communicator Carl Sagan, suggests that frequency of media interaction might be inversely proportional to scientific ability. Sagan's biographers, Keay Davidson and William Poundstone, both say that his popularization of science was a big reason that the National Academy of Sciences did not accept him as a member. And yet Sagan, as they document, had a prolific publication record and many protégés, including Squyres.

Finally, CIRM grantee Paul Knoepfler had this to say about why scientists should quit worrying about perception and start talking to the public. He wrote a blog entry about the need for scientists to get with the times in terms of communicating electronically. In a follow-up comment to his blog entry he wrote:

Scientists need to communicate in real time, or as close to it as possible, on the Internet. If they choose not to or are simply so unaware that they don't even know they should be doing this, they have lost out on an opportunity to not only to educate, but also to advocate. The anti-science groups out there have learned this lesson well.

CIRM held a media training at our annual grantee meeting last year in an effort to help grantees talk about their work. With all the misinformation about stem cells — regarding their origins and their therapeutic power — we need as many scientists as possible able to talk effectively about their findings.

Those rock stars of science communication might never have the name or image recognition as Debbie Harry or Bret Michaels, but we do hope they can be part of an effort to help people understand the power of science to create new therapies or technologies that improve our world and our lives. And to explain that science is just plain cool.

Both Jamieson and Knoepfler have been very effective communicators of stem cell science. In addition to other media work, they both worked with CIRM to create explanatory videos:

Paul Knoepfler: Tumor Formation in Embryonic Stem Cells
Catriona Jamieson: Therapies Based on Cancer Stem Cells 

A.A.

Top four list: why embryonic stem cells are critical

Yesterday CIRM grantee Bruce Conklin gave his top four reasons why embryonic stem cells are so valuable and why federal funding for the work needs to be able to continue. Conklin, who is Senior Investigator Gladstone Institute of Cardiovascular Disease and professor at UCSF, studies heart rhythm defects by creating iPS cells from people genetically predisposed to have those defects, then maturing those into heart cells in a dish. This gives him a way of studying the rhythm defect in the lab, and allows him to test drugs that might correct the arrhythmia. (You can see his New Cell Lines Award research summary here.)

Conklin says he’d never be able to carry out his iPS work without advances made with embryonic stem cells. Here’s his list:

1) Scientists have genetically engineered embryonic stem cells that are widely used for studying specific processes in the lab. “Obviously, we can remake those cells lines using iPS cells but it’s a huge waste of time,” he said. Instead of making progress toward developing new therapies or finding new drugs, labs would have to spend years redoing work they’ve already done.

2) Embryonic stem cells are farther along clinically than iPS cells or the new directly reprogrammed cells. “The first clinical trials of pluripotent cells will be embryonic stem cells. Ten years from now we’ll probably see a mix of embryonic and iPS cells,” he predicted. Adult cells are good for many things, he said, but aren’t as flexible as pluripotent embryonic or iPS cells.

3) Embryonic stem cells reproduce the steps taken by nature. “The idea is that nature knows something we don’t, because we don’t know very much,” Conklin said. Studying embryonic stem cells as they go down the path toward a specific cell type, like a skin cell or a neuron or a pancreatic islet cell, can give us clues about what might be going wrong in diseases afflicting those cell types.

4) Some diseases seem to begin at the earliest stages of development. “If we are going to understand human development we have to know how the process happens naturally,” he said. Only by studying embryonic stem cells can we understand genetic diseases that strike at the earliest stage, or what’s called epigenetic changes that can alter the way genes function.

Conklin seemed optimistic about the future of iPS and direct reprogramming, but pointed out that even Jamie Thomson, who was part of one of the two teams that first created iPS cells, has predicted that iPS cell research would be five years ahead of where it is now if embryonic stem cell research weren’t slowed under the Bush funding regulations.

The CIRM Governing Board recently passed a resolution that “strongly encourages federal policy that supports all forms of stem cell research for the millions of Americans who suffer from disease and injury and strongly supports criminalizing human reproductive cloning.” You can read Resolution 2010-01 here, which supports both the DeGette and Spector legislation “or any successor legislation that embodies the policies advanced in President Obama’s Executive Order 13505 and the National Institutes of Health July 7, 2009 guidelines on hESC research.”

A.A.

Mighty mice point to stem cell therapy for muscle diseases and aging

The L.A. Times gave it’s rodent of the week designation to a mighty mouse produced by University of Colorado, Boulder researchers.

The group transplanted muscle stem cells from healthy mice into mice with damaged muscles. Not only did the muscle stem cells spring to action, repairing the damaged muscle, but they maintained the mouse in its newly bulked up state for its entire two-year lifespan.

The Telegraph quotes lead author Bradley Olwin as saying:

"We found that the transplanted stem cells are permanently altered and reduce the ageing of the transplanted muscle, maintaining strength and mass."

"With further research we may one day be able to greatly resist the loss of muscle mass, size and strength in humans that accompanies ageing, as well as chronic degenerative diseases like muscular dystrophy."

In their story, the L.A. Times points out that the stem cells came from young mice and were implanted into similarly young mice. Other research by CIRM grantee Irina Conby at University of California, Berkeley has found that the environment in older mice somehow inhibits muscle stem cells from repairing damaged muscle (here's a blog entry on her work). Likewise, bathing muscle stem cells from older mice in the blood of young mice seems to rejuvenate the cell’s ability to repair tissue.

The issue of aging and environment is an important one when looking at transplantation of adult stem cells. Where the cells are implanted could play an important role in how well the cells repair damage. (You can read more about aging and stem cells in this story from Stanford University.)

As a runner prone to muscle damage and whose clock is relentlessly ticking, I'll be watching for researchers to figure out what it is that allows the transplanted stem cells to flourish and prevent aging in mice. And I can only hope the answer is not that I have to remain young for my muscle stem cells to thrive.

A.A.

November 14: World Diabetes Day

Guest bloggers Chris and Lorraine Stiehl are CIRM Patient Advocate Coordinators*:

Sunday, November 14 is World Diabetes Day. Back in 2004, we joined the team that launched Prop 71 because of the opportunity that stem cells may provide for diabetes. We are now involved with CIRM as Advocacy Coordinators, working with all of you across the state to help bring the exciting research made possible by CIRM to the patient advocacy community. In our short time in this role, we have met many passionate and dedicated stem cell advocates who are working hard to find better treatments and cures for dozens of diseases.

In honor of World Diabetes Day, we thought we’d make diabetes the subject of our first blog posting. As you know, diabetes is a growing epidemic in California and across the globe. CIRM has funded numerous research projects involving diabetes including a Disease Team Research Award granted to UCSF and ViaCyte (you can see a complete list of diabetes awards funded by CIRM). Not only are these researchers seeking to create an unlimited supply of insulin-producing beta cells from stem cells, they are exploring ways to protect these cells from attack by the patient’s own immune system. Now that these researchers have experienced success in animal models, they are excited about moving their research into pre-clinical and clinical application – thanks to CIRM funding. This goal is in sight.

The Centers for Disease Control (CDC) estimates that there are over 24 million Americans who are living with diabetes. Approximately 3 million of these individuals have type 1 diabetes, the most severe form of this disease. Voluntary health organizations such as the Juvenile Diabetes Research Foundation (JDRF), a major funder of Prop 71, and the American Diabetes Association (ADA), continue to promote stem cell research and partner closely with organizations such as CIRM.

In addition to supporting research, JDRF and ADA work hard to create a platform for the diabetes community to organize itself, so advocates may more effectively advance research at both the state and federal levels of government. Websites such as www.tudiabetes.org and www.juvenation.org provide opportunities for those with diabetes to build relationships with one another and find daily support. Translating the deeper connections made possible through social media into offline relationships is also critical. That is why JDRF is hosting Type 1 Talk on World Diabetes Day, November 14. Additionally, ADA is actively promoting World Diabetes Day and their activities may be found on their website.

As Patient Advocate Coordinators for CIRM, we hope to educate, excite and empower advocates involved in all diseases that demand a cell-based solution such as those found in stem cell research. We look forward to working with all of you in the coming months And if you want to keep up with stem cell research more broadly become a fan of CIRM on FaceBook.

Lorraine Stiehl also serves as the National Chair of Grassroots Advocacy for JDRF and was their Volunteer of the Year for 2010. She will be one of the speakers on the Type 1 Talk webcast.

* This entry was updated 11/16 to reflect the proper title for Chris and Lorraine Stiehl: "CIRM Patient Advocate Coordinators"

Stem cell model of autism allows testing of new drugs

Back in May 2009, CIRM held a workshop in which leading scientists discussed ways in which stem cell research could benefit people with autism (here is the autism workshop report from that meeting). I have two friends with children who are on the spectrum and have seen first-hand the toll the disease takes on the families.

This week, some CIRM grantees published an exciting paper that reflects the hopes of that workshop. The scientists took skin cells from people with a severe form of autism called Rhett syndrome, reverted those cells to an embryonic state, and matured them into neurons. The work was published in the in the November 11 issue of Cell. This is the first time scientists have been able to study what amount to autistic neurons in a lab dish.

It turns out they have some abnormalities, as you might expect. According to Technology Review:

They found that neurons derived from patients with Rett syndrome showed certain abnormalities, including markedly smaller cell bodies, dendrite connections, and decreased cell-to-cell communication.

The best part is that when the team from the Salk Institute and the University of California, San Diego exposed these neurons to a protein called insulin-like growth factor the neurons looked more normal.

This type of work is precisely what the workshop recommended as a starting point. Nerves grown from people with autism are an ideal environment for testing possible therapies and for understanding the disease. The group hopes to test therapeutic options suggested by these findings in mice, and to grow neurons from people with different forms of autism.

At this point the work is far too early to benefit my friends. The scientists still need to better understand the different forms of autism, study this proposed therapy in animals and understand the mechanism better before they can even begin thinking about a human trial. But for a disease that currently has so little clinical hope, even early stage work is a step in the right direction.

CIRM funding:
Fred Gage (RL1-00649-1 and RC1-00115-1)

Nobel prize winner Stanley Prusiner calls for Alzheimer's disease funding

Nobel Prize winner Stanley Prusiner was one of the authors on a letter to the New York Times on October 27 advocating that congress pass legislation that “would raise the annual federal investment in Alzheimer’s research to $2 billion, and require that the president designate an official whose sole job would be to develop and execute a strategy against Alzheimer’s.”

Prusiner, who is director of the Institute for Neurodegenerative Diseases at UCSF, along with retired U.S. Supreme Court Justice Sandra Day O'Connor and gerontologist/psychologist Ken Dychtwald, wrote:

As things stand today, for each penny the National Institutes of Health spends on Alzheimer’s research, we spend more than $3.50 on caring for people with the condition. This explains why the financial cost of not conducting adequate research is so high. The United States spends $172 billion a year to care for people with Alzheimer’s. By 2020 the cumulative price tag, in current dollars, will be $2 trillion, and by 2050, $20 trillion.

If we could simply postpone the onset of Alzheimer’s disease by five years, a large share of nursing home beds in the United States would empty. And if we could eliminate it, as Jonas Salk wiped out polio with his vaccine, we would greatly expand the potential of all Americans to live long, healthy and productive lives — and save trillions of dollars doing it.

Their letter came days after CIRM board member Leeza Gibbons joined California’s First Lady Maria Shriver in her first March on Alzheimer’s at the California Women’s Conference. Gibbons founded Leeza's Place to provide support for caregivers of people with Alzheimer's disease and other disorders. The march raised a quarter of a million dollars for Alzheimer’s research.

During Alzheimer’s disease awareness month here are some numbers to keep in mind, from the NYT letter:

Starting on Jan. 1, our 79-million-strong baby boom generation will be turning 65 at the rate of one every eight seconds. That means more than 10,000 people per day, or more than four million per year, for the next 19 years facing an increased risk of Alzheimer’s. Although the symptoms of this disease and other forms of dementia seldom appear before middle age, the likelihood of their appearance doubles every five years after age 65. Among people over 85 (the fastest-growing segment of the American population), dementia afflicts one in two. It is estimated that 13.5 million Americans will be stricken with Alzheimer’s by 2050 — up from five million today.

CIRM has a Alzheimer's disease fact sheet about stem cell therapies for Alzheimer’s disease, and a list of all awards addressing Alzheimer’s disease funded by CIRM. One of those grantees, Frank LaFerla, is in this video about a discovery he made as part of the CIRM-funded research.




A.A.

Stem cell research like picking stocks? We don't think so.

A story by Nick Wade in Monday’s New York Times rubbed some scientists the wrong way — and I must admit the piece was not too popular around CIRM headquarters.

Wade equated research funding with picking stocks. His idea is that a broad portfolio is bound to include some winners (he attributes this approach to the NIH and NSF) whereas attempts to only buy the big winners can produce a risky portfolio (an approach he attributes to CIRM).

Writing for the science portal Science 2.0, Michael White writes:

This is not right.* Wade goes astray in thinking of science in terms of hits and misses. Basic research is not like being at bat, with the occasional single base hit or home run being the exception in a sea of strikeouts.

Most research is simply conventional and incremental. Most of the time it's not a miss, a disaster, or a failure - it's a small, sometimes not too surprising addition to our knowledge of a subject. Most research projects and NIH grants end in success, not failure - but the successes are usually small. In fact, there probably aren't enough failures, because, unlike the venture capitalists Wade compares it to, the NIH is very unwilling to take risks in search of the spectacular winner. Funded projects are the ones almost guaranteed to work.

CIRM grantee Paul Knoepfler at UC Davis also takes objection to the piece. His point: CIRM isn’t just investing in one big thing. Three billion dollars to just fund one area of stem cell research, that would be narrow. But CIRM has funded an incredible range of research, from the most basic science to translational work, and in approaches spanning stem cell transplantation therapies to modeling disease, drug testing, and models of regeneration (the very research Wade suggests we should fund).

Knoepfler writes:

Clearly [Wade] knows very little about CIRM and about stem cell research. He makes the argument that because CIRM only funds research in 'a single field' that chances are high that Californians will lose out. First, he is wrong that CIRM only funds one field. The breadth of research funded by CIRM spans a few dozen fields from cancer biology to neurological disorders, to heart disease, diabetes, HIV/AIDS, etc. Second, Mr. Wade ignores the substantial accomplishments that CIRM has already made in just its first few years.

Where CIRM agrees with Wade’s piece is in his suggestion that we look to how animals such as zebrafish and newts naturally regenerate, and use that knowledge to improve human regeneration. Deepak Srivastava from the Gladstone Institutes, who has been looking at tissue regeneration in mouse hearts, is making tremendous progress in part through CIRM funding (here is his research summary), as is USC’s Gage Crump, studying zebrafish jaw regeneration as a model for bone regeneration (here is his research summary). 

For people interested in seeing the range of what CIRM has funded, we have this searchable list of all our funded stem cell research awards. We also have this list of our rounds of funding, explaining the role that funding plays in creating CIRM’s broad research portfolio.

A.A.

The next big thing -- and how to fund it

Gina Kolata had an interesting piece in today’s New York Times about the difficulty of predicting where the next big biomedical breakthrough will come. She, like many people, had predicted big things for gene therapy. She was wrong.

She writes:

But was I right to say advances are unpredictable? Yes and no, scientists say.

“I’ve learned over the years that the best predictor for what will be new and exciting is, ‘Expect the unexpected,’ ” said Dr. Joseph L. Goldstein, a Nobel laureate who is professor and chairman of the department of medical genetics at the University of Texas Southwestern Medical Center in Dallas.

Dr. David Baltimore of CalTech, another Nobel laureate, said, “If you could predict it, it wouldn’t be a breakthrough.”

She goes on to quote Dr. Richard Klausner, a former head of the National Cancer Institute, who says Moore's Law, which refers to the exponential increase in computer processing speed, also applies to biomedical research.

When that happens, Dr. Klausner said, “barriers and unknowns seem to be falling,” and it is pretty much predictable that even more exciting discoveries will be made.

He thinks that's where discoveries relating to stem cell fate are today. In fact, yesterday we wrote about yet another discovery in that area.

CIRM’s Basic Biology Awards are our answer to the problem of trying to fund the next big thing. (Here are recipients of the Basic Biology I and Basic Biology II awards.) The goal is to fund researchers looking into basic questions of how stem cells function, with the idea that the answers might lead to insights that generate new uses for stem cells. Those insights might be in the area of transplantation, but could also reveal new ways of developing drugs or understanding disease or controlling stem cell fate.

Or, the breakthroughs might be in an area that doesn’t yet have a name. Who knows?

A.A.

Human skin cells converted to blood

Over the past two years we’ve watched a series of scientists shoot down the prevailing idea that one adult cell type cannot be converted into a different adult cell, with researchers directly converting skin cells into insulin-producing cells, nerve cells and heart tissue. (You can see our blog entry on this work here.)

A Canadian team has become the most recent to prove that idea false, directly converting human skin cells to blood cells. The work, by a group at McMaster University in Hamilton, Canada, is the first to show that human cells are capable of such transformations, and is the first to create progenitor cells, which can form all types of cells within a given tissue.

The work was published online November 7 in Nature, which also ran a news story about the work:

Mickie Bhatia, a stem-cell researcher at McMaster University in Hamilton, Canada, and his colleagues chose to make blood progenitors from skin cells because red blood cells created from stem cells do not make the adult form of haemoglobin. "Those cells, because they think they're embryonic, make embryonic and fetal blood," he says.

They also quote the scientist responsible for creating Dolly the sheep Ian Wilmut as saying:

"It takes us a step along the line to believing that you can produce anything from almost anything."

It could be many years before this discovery is being transfused into the first human patient. The group used a virus to introduce new genes into the skin cells, which is problematic for human transplantation. They also need to prove in the lab and in animals that the blood cells they’ve produced can actually replace the function of human blood.

When Yamanaka first created iPS cells in 2007, CIRM almost immediately saw a surge in grant applications proposing to incorporate or improve on the technique. Now more than 50 of our funded awards involve human iPS cells (you can see that list here). Over the next few rounds of grant applications it will be interesting to see how many new researchers incorporate direct reprogramming into their proposals.

A.A.

Food begets stem cells?

Drosophila intestinal stem cells (ISCs)
respond to nutrient availabilityImage:
Courtesy of Dr. Lei Wang,
Salk Institute for Biological Studies

Researchers at the Salk Institute for Biological Studies have found an intriguing connection between stem cell behavior and food. The more food, the more stem cells, and those stem cells divide more vigorously.

The researchers did their work in flies, which provide a ready laboratory for studying tissue stem cells in their natural environment. Flies have a pool of stem cells in the testes and in the intestine that are easy to monitor under different conditions and that mimic similar cells in our bone marrow, liver or muscles in their capacity to rebuild tissue.

What they found is that in flies fed a poor diet, the stem cell pool in the testes and intestines dwindled and those remaining cells divided sluggishly. Improving the flies’ diets rebuilt the stem cell pool. It appears that the protein insulin, which is present in the blood after a meal, is what signals stem cells about the presence or absence of food. The findings are published in the Nov. 4, 2010, online edition of the journal Current Biology.

In a press release, Salk writes:

"Tissues that are maintained by stem cells respond to adverse environmental conditions by reducing the overall number of stem cells, as well as the activity of those stem cells, but maintain them in such a state that they can respond quickly and effectively once the nutritional conditions become more favorable," says Leanne Jones , Ph.D., assistant professor in the Laboratory of Genetics, who led the study.

Symmetric division of male germline
stem cells (GSCs) in a Drosophila testisImage:
Courtesy of Dr. Catherine McLeod,
Salk Institutefor Biological Studies

Jones has a New Faculty Award from CIRM, although this study is not part of her grant. Salk went on to write:

Jones and her team think it likely that the link between insulin signaling and stem cell response will turn out to be important not only for nutrient deprivation but also for other situations where a body's metabolism might be altered. "One may think of how tissue homeostasis is modified in a situation when the body cannot accurately monitor or utilize available nutrients-for instance, in case of a person who is diabetic," says Jones.

They also hint that if the presence or absence of food can alter stem cell behavior, perhaps dramatic changes in diet could be incorporated into therapies.

Following on the heals of Halloween, here’s hoping chocolate turns out to be a food that brings out the best in stem cells.

A.A.

A salute to caregivers from Leeza Gibbons

At CIRM we want nothing more than to find cures for the diseases that afflict people around the world. Until that day comes, many of the diseases we hope to cure — Alzheimer’s disease, Parkinson’s disease, spinal cord injury, ALS, to name a few — place an incredible burden on the caregivers in addition to the patients themselves.

Caregivers have no greater advocate than Leeza Gibbons, who also serves on the CIRM governing board. Her online caregiver support network, Leeza’s Place, is celebrating National Family Caregiver Month with events throughout the country to both support and educate caregivers. A list of those events is available here.

On her blog, Leeza wrote:

At Leeza’s Place, we know the job of being a caregiver is both frustrating and fantastic; isolating and invigorating; a blessing and a burden. Those husbands and wives, daughters, sons and friends who care for someone they love often find they are stronger than they ever imagined they could be.

As we celebrate those courageous spirits, we offer respect and gratitude to all who are on the front lines of humanity. A month recognizing caregivers is just a starting point for us to create more national awareness, better support, respite and care. At Leeza’s Place, this month (and every month) we offer hugs of support, approval and a blanket of love!

To hear more about Leeza’s Place and Leeza’s caregiving mantra of “Take Your Oxygen First” visit their online media page here.

Here is Dan Desmond, who has ALS, paying a touching tribute to his wife and caregiver, Gloria Desmond.



A.A.

Federal stem cell legislation unlikely in lame duck session

Science had a story this morning about what yesterday’s elections mean for stem cell funding. In it they suggest it’s unlikely that the lame duck congressional session will bring legislation to expressly legalize federal funding for human embryonic stem cell research, writing:

"I don't think it's going to be a priority for them," says Jennifer Zeitzer of the Federation of American Societies for Experimental Biology in Bethesda, Maryland. Her bottom line: "The outlook for stem cells is even less certain now than it was yesterday."

A legal challenge to federal funding for human embryonic stem cell research is set to be heard Dec. 6. Until then, the NIH is continuing to fund existing grants that involve human embryonic stem cells, but is not giving out new awards. Some CIRM grantees including Joanna Wysocka of Stanford University and Paul Knoepfler of UC, Davis have received scores on NIH proposals that would normally result in getting grants funded. Instead, they are putting projects on hold that could lead to insights in developmental disorders and tumor formation.

Wisconsin, which the home of the first human embryonic stem cell line, voted in both a governor and senator who oppose the research their state helped create.

A.A.

15 registered stem cell lines and counting

Guest blogger Geoff Lomax
Senior Officer to the Standards Working Group

CIRM reached an important milestone with the recent registration of a 15th human embryonic stem cell line created with institute funding. (Here is a description of how researchers create human embryonic stem cell lines.) In approving Proposition 71, the citizens of California entrusted CIRM to support safe and responsible stem cell research. A major early accomplishment for the institute was the development of standards requiring review and oversight of work involving stem cell line derivation. Here is a list of all CIRM registered lines.

The registration process it a testament to CIRM’s grantees commitment to these standards. To be eligible for registration, a responsible official must certify the line was created under a protocol that meets CIRM’s exacting requirements for review, informed consent and voluntary donation. In addition, the research team must certify the approved protocol was followed. This dual certification serves to put researchers and oversight officials on the same page – both literally and figuratively. The result is a common understanding of expectations throughout the research community.

Registration also supports the sharing of cell lines. Cell lines derived according our requirements are automatically eligible for use by CIRM-funded researchers. This process addresses a longstanding need of our grantees – the creation of a list of eligible hESC lines.

The latest lines were created at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at the University of California, Los Angeles. UCLA is currently working on an agreement for the distribution of the lines to outside researchers. UCLA will distribute the lines to outside investigators who provide evidence their research is approved by an appropriate research oversight committee. It is great to see UCLA taking steps to advance responsible stem cell research.

G.L.

Miniature liver grown from stem cells

Researchers from Wake Forest University Baptist Medical Center have created a tiny, functional liver grown from stem cells. It's not big enough to process a half-time beer (Go Giants!), or much of anything else, but it's an interesting start.

The researchers presented their laboratory-grown liver, which is about the size of a walnut, at a meeting of the American Association for the Study of Liver Diseases.

Growing fully formed organs out of stem cells is thought to be a distant goal of stem cell research. That's because of the complexity of organs. Of the possible stem cell therapies that are expected to reach clinical trial, most involve transplanting a single cell type -- retinal cells for macular degeneration, nerve support cells for spinal cord injury, or insulin-producing cells for diabetes. Whole organs contain a complicated network of cell types that all have to work together in order for an organ to function.

The Wake Forest group took an existing liver and stripped it of all the liver cells, leaving behind the support structures like connective tissue and blood vessels. Onto that they placed liver stem cells, which then grew in a bioreactor to create a tiny new liver.

The BBC quotes Shay Stoker, who led the research, saying there's a long way to go before this tiny proof-of-principle is ready to replace organ donations:

"Not only must we learn how to grow billions of liver cells at one time in order to engineer livers large enough for patients, we must determine whether these organs are safe to use."

That's many years of laborious time in the lab condensed into a single sentence. Scaling the liver up and proving its safety will be significant hurdles. Still, it's exciting to see these first steps toward what might one day be an alternative for thousands of people currently waiting on donated organs. 

A.A.

More stem cell research space = jobs and therapies

The Lorry I. Lokey Stem Cell Research Building

We’re in the middle of a big week for CIRM-funded research facilities. UCLA opened the doors to their new CIRM-funded stem cell research space Monday (here's a video about that building) and today Stanford cuts the ribbon on the largest of the CIRM buildings — a gleaming 200,000 square-foot state-of-the-art facility. According to the Stanford press release about their Lorry I. Lokey Stem Cell Research Building:

The building’s 200,000 square feet of floor space, serving about 550 occupants, makes it the largest dedicated stem cell research building in the country, if not the world. But just as important, it was financed without any federal funding — buffering its occupants to some degree from the vagaries of embryonic stem cell politics. 

The buildings are part of CIRM’s Major Facilities RFA, given out in May 2008 when federal funding could only be spent for stem cell research involving a small number of approved cell lines. That included working with unapproved lines in buildings created or supported through federal funds, which ruled out most available research space for work involving unapproved human embryonic stem cell lines. The CIRM buildings provide space free and clear for working with whichever stem cell lines scientists think will move the field toward new cures.

CIRM awarded $271 million to 12 institutions, each of which was required to raise additional funds through private donations. Altogether, CIRM’s investment brought in an additional $800 million in financial commitments and created construction jobs throughout the state at a time when those jobs were very much needed. This week's building openings came about thanks to a $20 million donation to UCLA and a $30 million gift to USC by The Eli and Edythe Broad Foundation and a $75 million gift from Lorry I. Lokey to Stanford University.

Following today’s ceremony at Stanford, the University of Southern California will hold their grand opening Friday. Altogether, those three buildings created 322,000 square feet of new research space, all of it free of federal funding and therefore available for research into all types of stem cells regardless of what happens with the current court cases. This space has the capacity to house nearly 1,000 members of research teams.

Stanford gave a nice description of how having stem cell researchers housed together in well equipped space will speed the research that takes place. They quote Theo Palmer, who works on stem cell therapies for neurodegenerative diseases:

“We used to have to plan our day around getting our samples where they needed to be when they needed to be there. Now some of the best resources in the world are immediately available — including extraordinary cell-sorting capabilities and some of the most advanced single-cell genetic-profiling equipment. At other places in the country these resources are essentially not available, or available only by special arrangement.”

That time saved means CIRM grantees can work faster than ever toward new disease therapies.

-A.A.

Victoria-California stem cell collaboration tames the immune system

The Victoria, Australia, innovation Minister Gavin Jennings is talking up a Victoria-California research team working to develop a therapy for autoimmune diseases such as type 1 diabetes and multiple sclerosis.

“The project highlights the value of collaboration between world-leading centres like Victoria and California in biotechnology and stem cell research. It is yet another demonstration of our commitment to take action to improve the quality of life for millions of people around the world.”

The team is one of CIRM’s Transplantation Immunology Awards, this one led by Kenneth Weinberg at Stanford University (read a summary of their project). In that same round of funding a Victorian scientist teamed up with Scripps Research Institute’s Jeanne Loring.

CIRM has formed collaborative partnerships with ten organizations in U.S. States or internationally. These are intended to build partnerships between leading stem cell scientists, wherever they may be working. As a state agency, CIRM’s money only goes to the California researchers, with our partners supporting their scientists. So far it’s been a very successful program, with 14 awards including international research partners in Canada, Germany, Japan, the U.K., and Victoria, Australia. You can find those awards on our stem cell grants table.

In the project Jennings discussed, the researchers are looking for a way of regulating the immune system, which causes autoimmune diseases when it attacks the body’s own organs and tissues.

“This project is critical to us learning more about how to regulate the immune system in a bid to enhance the potential of stem cell derived tissue transplants as therapies to combat MS and other conditions.”

A.A.

The CIRMy's: Top awards to stem cell videos

On January 16, 2009 CIRM began our glamorous TV career, launching the YouTube channel CIRMTV. Despite our fabulous onscreen talent the Emmys have yet to call (though they are welcome to comment below...). Still, we’re pretty pleased with the channel’s success. Today we reached 100,000 views to our videos, which include some educational pieces about stem cell research and a disease-focused series about individual conditions that CIRM-funded researchers are working to address.

Overall, our videos are most popular in the U.S., Canada, the U.K., Australia, the Philippines, and Sweden. The top ten views have gone to:

1) Parkinson's Disease: Progress and Promise in Stem Cell Research

2) Hans Keirstead: Developing therapies based on embryonic stem cells

3) Jerome Zack: Creating iPS Cells

4) Macular Degeneration: Progress and Promise in Stem Cell Research

5) Irv Weissman: Differences between Adult and Embryonic Stem Cells

6) Bringing Stem Cell Cures to the Clinic: UC Davis GMP Facility

7) Catriona Jamieson: Therapies Based on Cancer Stem Cells

8) Paul Knoepfler: Tumor Formation in Embryonic Stem Cells

9) Huntington's Disease: Progress and Promise in Stem Cell Research

10) CIRM Major Facilities Speed Stem Cell Science and Create Jobs

I’m going to give an editor’s choice award to a video we made about our Bridges to Stem Cell Research program. The passion these students have for stem cell research and for their future careers is exciting to see:

CIRM Bridges Award: Building California's Stem Cell Research Workforce 

A.A.

Knocking out leukemia stem cells

A good report about bone marrow transplantation in progress comes from the National Hockey League, of all places. Mandi Schwartz, a Yale women’s hockey player, was diagnosed with acute myeloid leukemia and is being treated at the Seattle Cancer Care Alliance.

In the name of full disclosure, that’s the center that cured my mother’s lymphoma, so let’s just say I’m a fan.

NHL.com wrote a nice description of how bone marrow transplantation knocks out leukemia stem cells. Acute myeloid leukemia is a cancer that begins in the bone marrow stem cells — the cells that continuously produce new blood and immune cells throughout a person’s life. A bone marrow transplant essentially replaces the cancerous leukemia stem cells with new ones from a donor, like an organ transplant but with bone marrow. The NHL writes:

Engraftment, which was the next phase in her recovery, is needed in order for the transplanted stem cells to begin to grow in her bone marrow and manufacture new blood cells and immune cells... Complete recovery of a new immune system can take a year or longer depending on any complications as a result of the transplant.

Bone marrow transplants like this one are effective, but dangerous. The process of eliminating a person’s diseased bone marrow leaves the person extremely weak and prone to infections. This danger is why several CIRM grantees are working on a less toxic way of killing off the diseased bone marrow stem cells (here's a list of our awards targeting blood cancers). Irving Weissman at Stanford University has found molecules on the surface of the stem cells underlying acute myelogenous leukemia. He has a CIRM disease team award to develop a chemotherapy that could destroy those cells in a way that’s far less toxic than bone marrow transplant.

If that research is successful, future people like Schwartz may recover from acute myelogenous leukemia with fewer side effects. As someone who has seen a family member battle cancer, fewer side effects for an effective therapy is a winning combination.

A.A.

Basic research and the search for cures

Two interesting reports today discuss the relationship between basic research and the kind of translational research that is the most visible sign of progress toward cures.

In his blog, the director of the bay area biotech collaborative QB3 Regis Kelly writes about public speakers at the Translational Medicine Alliance speaking out against basic research. He says:

Repeatedly mentioned with disdain was the amount of money that went into R01 grants, the single investigator grants that are the backbone of fundamental research in the US. Over 80% of the grants go to R01s, it was said, while only 2 to 5% go to translational research, the mantra of the meeting participants.

This is the same type of research funded by CIRM’s Basic Biology Awards and in some New Faculty Awards. The basic discoveries that come out of this kind of research are considered to be the fuel in the pipeline leading to new cures: No new ideas? No new therapies.

Kelly advocates rather than ignoring the complaints, “put our house in order and mount a major public education campaign to validate our position.” That is, do what can be done to make basic research as efficient and effective as possible then explain to members of the public just what they are getting for their money.

Or we can discount the criticisms as uninformed foolishness, and do nothing. That could be suicidal!

Kelly’s point is a good one. Most people have at least one friend or family member with a critical disease, and those people want to see new cures coming from publically funded research. Until the relationship between basic research and new cures is made clearer people will likely continue pushing for less basic research.

While Kelly defends basic research, the head of the National Cancer Institute Harold Varmus held a brainstorming session to figure out the basic questions in cancer research. According to Science magazine:

Once the list is finished, Varmus might hold a special competition to invite proposals for several questions and fund, say, 15 of the best ideas. Research funding may be tight, but "we've got over a $5 billion budget," Varmus says. Nothing has been decided, though. Right now, he says, "we're just trying to have a conversation that evolves into something useful."

Stanford’s Irv Weissman, who was at Varmus’ session, gave an excellent talk to the CIRM governing board about the value of basic research. In his case, it was a basic discovery about stem cell biology that led to cancer research that’s now moving toward the clinic.