Full Vision Cure? Full Stem Cell Research Required

By Don C. Reed

The world is delighted that patients with injured eyes in Italy regained their sight, thanks to the use of stem cells transplanted from their own good eyes. This is a wonderful victory for Dr. Grazziella Pellegrini, the University of Modena, and everyone involved. They are doubly to be congratulated because they are working with one hand tied behind their backs. In Italy, it is illegal to fund embryonic stem cell research. So they did what they could with what was allowed.

To give sight to someone who has been blinded in one eye is wonderful indeed.

But to claim this success invalidates the need for embryonic cells, which some have done, would be wrong.

First, the improvement only works on injured eyes, not those damaged by disease or genetic problems. This disqualifies the overwhelming majority of blindness sufferers, such as people with macular degeneration or retinitis pigmentosa. Also, not every injury can be treated. Everything depends on the patient having enough good tissue from the eye to draw cells from. It would be useless to a person born blind.

It has also been reported that another scientist was not able to duplicate Dr. Pellegrini’s success. According to a story in Bloomberg News Dr. Ivan Schwab, an ophthalmology professor and stem cell researcher at UC Davis:

“…has treated patients in clinical trials with a procedure based on Pellegrini’s work. While his patients improved for a time, the benefits didn’t endure.”

Adult stem cell work has been studied for more than half a century; it would be shocking indeed if there were no successes. This particular study began in 1998—the same year human embryonic stem cells were first isolated.

As the father of a paralyzed young man (Roman Reed, inspiration for a California law which has funded embryonic stem cell research) I follow the research closely. This fall, we hope, an embryonic stem cell treatment will go to human trials.

Adult stem cell research is a useful tool. But it is only one tool, not the toolbox.

Patient advocates, like the vast majority of scientists, support full stem cell research, not any single kind to the exclusion of all others.

Don C. Reed
Citizen-sponsor, Roman Reed Spinal Cord Injury Research Act

Stem Cell Tourism in the news

The issue of stem cell tourism has gotten a lot of attention in the past few weeks. Two weeks ago, the Costa Rica health ministry closed down a clinic offering unproven stem cell therapies (here is our blog entry on this event, and a video about stem cell tourism). Last week, CIRM and ISSCR co-hosted a public seminar on stem cell tourism, at which the ISSCR revealed their fantastic new site alerting the public to the issue of stem cell tourism.

The new ISSCR site has some useful content, but also allows people to enter the name of a clinic which the ISSCR will then investigate and report on. People should bookmark the site and pass it along to friends or family members who are considering traveling for unproven stem cell therapies.

Finally, last week a woman died from complications resulting from a stem cell transplant in Thailand to treat a kidney disease. Many publications carried stories about her death, including Discover, which wrote:

The woman suffered from lupus nephritis, a disease in which the immune system attacks the kidneys. When medications no longer controlled her disease, she went to a still-unnamed clinic in Bangkok where doctors said they could treat her disease using stem cells drawn from her own bone marrow.

New Scientist and Nature also both carried stories about this case.


Shinya Yamanaka receives Kyoto prize for reprogramming skin cells

Last week, while stem cell researchers from around the world congregated in San Francisco for their annual meeting, stem cell pioneer Shinya Yamanaka won the Kyoto Prize for Advanced Technology. This award in generally considered to be a precursor to a Nobel Prize.

A press release from UCSF said:

Yamanaka received the prize for his discovery of a method of reprogramming adult skin cells to become embryonic-like stem cells. The discovery has opened up the field of stem cell research and dramatically changed the field of cell biology. He also is affiliated with and has a research lab at Kyoto University.

Yamanaka has a lab at the Gladstone Institute of Cardiovascular Disease in San Francisco, which is affiliated with UCSF. He does not have CIRM funding, but the Institute does have shared lab space funded by CIRM for carrying out stem cell research.


CIRM grantee Joanna Wysocka wins Outstanding Young Investigator Award

Some happy news from this week’s meeting of the International Society for Stem Cell Research held in San Francisco (co-sponsored by CIRM): CIRM grantee Joanna Wysocka won the organization’s Outstanding Young Investigator Award, given out at a session on Thursday morning. Wysocka, who is assistant professor of developmental biology at Stanford University School of Medicine, has SEED and New Faculty Awards to study how cells determine their eventual fate in a developing embryo.

In her acceptance speech, Wysocka credited CIRM with directing her work toward stem cell research. After receiving her award, she discussed some of her recent work, described in a recent blog entry from Stanford:

She went on to discuss her recent work in identifying the molecular cause of a human disorder called CHARGE. She also showed how her team has since used an analytical program created by Stanford developmental biologist and computer scientist Gill Bejerano, PhD, to identify more than 2000 sites on DNA that may affect the activity of a special type of cell called a neural crest cell. 

Congratulations to Wysocka and to Stanford!


Cancer genes also involved in embryogenesis, stem cell maintenance

CIRM grantee Paul Knoepfler at UC Davis just published an interesting paper. He also publishes a blog, so we’ll let him describe this findings in his own words:

We just published a paper supported by CIRM funding showing that knocking out c- and N-myc in mESC leads to a wave of differentiation-associated gene expression, decreased cell cycling, and a moderate elevation of apoptosis.  The myc-deficient mESC also fail to contribute to early embryogenesis. This is the first analysis of a role for myc genes in early embryogenesis.

We think that in part that Myc contributes to iPS formation by repressing differentiation-associated gene expression (ala Sridharan, et al).

So to induce pluripotency Myc appears to be doing what much the same job as it does to maintain pluripotency in ESC.  A role in cell cycle is also involved.

Differentiation, May 26, 2010
CIRM Funding: Paul Knoepfler (RN2-00922)


Stem cells deliver anti-cancer therapy to treat glioma

Looks like the FDA agrees with our choice of grantees. They’ve approved a clinical trial based on work led by Karen Aboody (shown in photo) at City of Hope using neural stem cells to target and kill high-grade gliomas. She’s the leader of a CIRM disease team that we funded to develop a second generation version of this therapy.

The clinical trial will test a genetically altered human neural stem cell line with a known tendency to migrate toward tumors. Those cells contain an enzyme, which accumulates where those stem cells congregate in the neighborhood of the tumor. When the patient is given a relatively harmless chemical called 5-FC, the enzyme converts it to an active chemotherapy agent just at the location of the tumor.

In a press release, the City of Hope quotes Karen Aboody as saying:

“Using neural stem cells as delivery vehicles for therapy may allow us to target concentrated therapeutics specifically to tumor sites while reducing the undesirable side effects of current chemotherapy regimens, including toxicity to normally dividing bone marrow, gastrointestinal tract, skin and hair cells.”

Bettina Steffen, M.D., who leads CIRM’s disease team program, says Aboody’s disease team project uses the same cell line that’s also used in the trial that just got FDA approval. That means when she’s ready to go to the FDA for her disease team work, there will be prior experience with the cell line. “Hitting all the hurdles to get the cell line approved is actually a huge deal, as this facilitates her path to the clinic with the CIRM-funded disease team program,“ Steffen says.

You can read more about stem cell approaches to treating glioma on CIRM’s glioma facts page.


Stem cells, Id, and cancer

Sanford-Burnham Medical Research Institute posted an interesting item today on their blog Beaker about a talk given as part of the Southern California Stem Cell Consortium. At the invitation of Evan Snyder, Dr. Antonio Iavarone of Columbia University discussed his work with a protein named Id. According to their entry:

He described how Id keeps stem cells as stem cells – increasing in number, but not settling down and choosing a specialty. When Dr. Iavarone and his colleagues turned Id off, stem cells were allowed to stop dividing and start differentiating.

“We are now beginning to screen chemical libraries to find molecules that target Id,” Dr. Iavarone explained. “We believe anti-Id agents will be effective at inhibiting tumor growth.”

 This type of work will be critical for developing therapies to combat cancer or replace damaged neurons in neurodegenerative diseases.


Costa Rica strikes against false hope

Many people in the stem cell community and at CIRM have been concerned about the growing trend of stem cell tourism — people going overseas to receive unproven “stem cell” therapies. The term Stem Cells is in quotes here because in general these clinics are less than open about what, exactly, the therapy entails. One tourism destination in Costa Rica owned by an Arizona entrepreneur was just shut down by the country’s Health Ministry. According to a story in Reuters the treatments cost between $5,000 and $30,000.

We’d love nothing more than to see people truly healed by stem cell therapies, but the only way to get there is through good research and clinical trials that prove a therapy’s safety and effectiveness. Clinics such as the one in Costa Rica profit off of people’s hopes without offering a verifiably effective therapy.

The International Society for Stem Cell Research provides some helpful information on stem cell therapies, and how to avoid clinics that misrepresent what their therapies can do. You can download it here: http://www.isscr.org/public/

We also have a video with CIRM grantee and Scripps faculty member Jeanne Loring discussing her concerns about the practice of stem cell tourism.

If you want to learn more about stem cell tourism you can attend the public seminar in San Francisco on June 15, in which a panel of stem cell scientists will discuss with the audience the safe path to the clinic. Information about that panel is available here. A video of that discussion will also be posted on the CIRM web site.


Multilayer retinina created from embryonic stem cells

More news from UC Irvine, this time relating to retinal diseases such as macular degeneration, retinitis pigmentosa, and Stargardt’s disease. A group led by Hans Keirstead of the Reeve-Irvine Research Center and the Sue & Bill Gross Stem Cell Research Center created an 8-layer retina from human embryonic stem cells.

In a press release, Keirstead said:

“What’s so exciting with our discovery is that creating transplantable retinas from stem cells could help millions of people, and we are well on the way.”

According to the release, more than 10 million Americans suffer from macular degeneration, the leading cause of blindness in people over 55. About 100,000 have retinitis pigmentosa, a progressive, genetic disorder that usually manifests in childhood.

Keirstead’s is one of several groups of CIRM-funded researchers trying to create functional retinas for transplantation. This video describes work by Mark Humayun at the University of Southern California.

You can see beautiful images of retinal tissue created from embryonic stem cells on the CIRM Flickr photostream.


Mysteries of stem cell migration revealed

CIRM-funded Researchers at the University of California, Irvine published an interesting paper this week that helps explain one mystery — how do transplanted stem cells go to the right place? This is an important issue for diseases such as multiple sclerosis, where transplanted stem cells would have to navigate to the damaged nerves.

In a press release, senior author Thomas Lane (shown in photo) said:

“Previously, we’ve seen that adult neural stem cells injected into the spinal column knew, amazingly, exactly where to go. We wanted to find what directed them to the right injury spots.”

What the team found is that in mice with an induced form of MS, transplanted neural stem cells responded to signals being sent by inflammatory cells at the site of the damage. The neural stem cells responded to those signals by migrating to the right place and maturing into a type of nerve cell called an oligodendracyte, which could help heel the disease.

According to the press release, three weeks after the initial treatment, 90 percent of the cells had grown into fully formed oligodendrocytes.

Proceedings of the National Academy of Sciences, Online Edition, June 1
CIRM Funding: Kevin Carbajal and Christopher Shaumburg (T1-00008)