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.