Stem cell banking workshop explores ethical and policy issues

At the 2010 Stem Cell Banking Workshop on May 26, CIRM president Alan Trounson discussed the potential value of a cell bank designed to support the needs of researchers and industry. Many of the participants believe there would be great scientific value in a bank that could provide a common approach to cell collection and distribution.

The workshop was designed to give special attention to ethical concerns related to the collection, creation, use and sharing of stem cells. Foremost, were ethical concerns about how to tell potential donors about how there cells will be used.  This process refereed to as “informed consent” is the cornerstone of research ethics. Participants agreed donors need to understand to the following:

•    What type of experiments there cell may be used in
•    How there privacy will be protected
•    Whether or not they would get any medical benefit from donating
•    Whether they can discontinue participation in the future (e.g. withdraw from the bank)

The workshop was not designed to answer these questions, but rather explore how these issues are being addressed already and consider how CIRM may adopt best practices. CIRM staff were asked to provide a report in the future. Workshop panelists included leading researchers and cell banking organizations. They provided cogent recommendations and offered concise insights for how these issues can be addressed.

In addition, they provided estimates of the costs and organizational capacity needed to run a cell bank. Overall, the workshop achieved its primary goal and served to stimulate discussion on a range of ethical and policy issues. A complete transcript will be available in June 2010.

- Geoff Lomax
Senior Officer to the CIRM Standards Working Group

Between Mice and Men, a New Type of Stem Cell

Humans and other non-human primates stand out from their fellow mammals in many ways, but notably by having one particularly oversized area of the brain. This area, the outer subventricular zone (OSVZ) feeds migrating neurons to the neocortex the seat of sensory perception, spatial reasoning, conscious thought and language. Scientists always assumed the OSVZ must have its own source of stem cells if, in the developing brain, it is supplying neurons for such a broadly vital area of the human brain. They have now found them.

Arnold Kriegstein’s team at UCSF used discarded fetal tissue to monitor cellular activity at various stages of development using a new labeling and tracking technique. They found the OSVZ to be a hub of cell proliferation. The newly found stem cell type goes through asymmetrical division producing a copy of itself and a daughter cell that is further along the path to becoming a neuron. That cell then goes through many rounds of symmetrical division producing many copies that can all then go on to become the desired neuronal cells needed in the neocortex.

A press release issued by UCSF on May 24 noted that the understanding provided by this model could shed light on many developmental brain diseases such as autism and schizophrenia. Kreigstein is quoted saying this understanding is critical:

“If we’re going to understand how these disorders develop, we have to better understand how the human and primate cerebral cortex develops.”

Understanding this developmental pathway will also inform efforts to direct neural stem cells to become the replacement cells of choice for various therapies.

D.G.

Nature, March 25 2010
CIRM Funding: Arnold Kriegstein (RC1-00346-1), Jan Lui (T1-00002)

iPS cells and embryonic stem cells -- similar but not the same

In the most recent face-off between iPS and embryonic stem cells, the ES cells came out ahead -- turns out iPS cells aren't the same as ES cells even when they carry the same mutation. That's according to work published in the May 7 issue of Cell Stem Cell.

(The image shows colonies of embryonic and iPS cells, taken taken in the lab of Jeanne Loring at The Scripps Research institute.)


First some background. Embryonic stem cells come from 5-6 day old embryos left over after in vitro fertilization. These primitive cells can turn into all cells of the body. iPS cells come from adult cells -- most often the skin -- that are reprogrammed to act like embryonic stem cells. They can also form all cells of the body. When iPS cells were first created in 2007 by Shinya Yamanaka, the prevailing wisdom was that they might one day completely replace ES cells, but only if they are safe and are truly equivalent to their embryonic counterparts.

That "but" has been the source of ongoing experiments, many by CIRM-funded researchers, who have found that the two cell types have different genes active (see this blog entry). In this latest work, the European and Israeli researchers found that when they created iPS and ES cells both containing a mutation that causes fragile X syndrome, the two resulting groups of cells behaved very differently, with the iPS cells not even activating the mutated gene.

This finding raises questions about whether iPS cells will be the best choice for mimicking diseases in a dish.

In an article in Medical News Today, Nissim Benvenisty, director of the Stem Cell Unit at the Hebrew University of Jerusalem and a leading author of the study, says:

"Until we understand better the differences between these two types of cells, the optimal approach might be to model human genetic disorders using both systems, whenever possible".

That said, when Stefan Heller of Stanford University created ear hair cells from both ES and iPS cells he found no difference in their functionality.

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UC Irvine Opens the Sue & Bill Gross Hall

On Friday, May 14 UC Irvine held the grand opening of their newly constructed Sue &Bill Gross Hall. According to a story on the University's web site:

The $80-million, 100,000-square-foot building was designed to facilitate contact between patients in the first-floor clinic and rehabilitation center and stem cell researchers in first-, second- and third-floor labs.

(Image: Hans Keirstead greets Bill Gross at the opening ceremonies. Courtesy of Daniel A. Anderson / UCI)

This was one of 12 facilities throughout California that received a CIRM Major Facilities Award to construct space for stem cell research. UC Davis opened their facility in March. Although Irvine held the second opening, theirs was the first for a newly constructed building.

The 12 major facilities received $272 million from CIRM, with private donations and institutional investments bringing the project totals to more than $1 billion. Sue and Bill Gross made a $10 million gift to the Irvine facility. An independent review of the impact of this investment for the state economy last year by The Analysis Group suggested that the projects would create 13,000 job years of employment and $100 million in tax revenue.

UC Irvine leveraged their CIRM dollars beyond their original goals -- they managed to construct a fourth floor for the same cost as the original three floor proposal.

An LA Times story quotes UC Irvine Stem Cell Research Center director Peter Donovan as saying:

"Whatever we achieve here, it is your legacy as much as ours," he said. "The use of stem cells can revolutionize the treatment of human diseases and injuries."

Scientists are due to move into the building over the next few weeks.



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Hairs in a Dish Give Hope to Damaged Ears

The microscopic hair cells found in the inner ear are so sensitive to vibration they can relay to the brain whether the air movement around them is from guitar licks by Eric Clapton or a piano chord from a Chopin Palinais, but too many loud Metallica concerts can damage them leading to hearing loss. Now, a team of stem cell scientists at Sanford has succeeded for the first time in growing these sensory cells from embryonic or iPS cells in a laboratory dish (shown in the image, taken in the laboratory of Stefen Heller at Stanford University), a key step in understanding how they really work and to growing new cells to replace damaged ones.

The team lead by Stanford’s Stefan Heller coaxed mouse embryonic stem cells in a dish into maturing into cells that looked and acted like the animal’s inner-ear hair cells. A press release from the university quoted Harvard neuroscientist David Corey, who was not connected to the study, offering hope and calling for patience:

“This gives us real hope that there might be some kind of therapy for regenerating hair cells. It could take a decade or more, but it is a possibility.”

The researchers accomplished this feat with both embryonic stem cells and stem cells created by reprogramming skin cells, so called iPS cells. They used various growth factors to first coax embryonic or iPS cells into becoming ectoderm, the embryo’s outer layer, then coaxed those ectoderm cells into progenitor cells for the ear and then into the hair cells.

Heller works on two paths toward curing deafness: drug therapy to resurrect the malfunctioning hair cells and stem cell-derived cell transplants. His team’s hairy dish could speed work for both. In the release he said:

“We could now test thousands of drugs in a culture dish. It is impossible to achieve such a scale in animals.”

It's exciting to see how far this research has come since 2008, when CIRM hosted a Spotlight on Deafness, with talks by clinicians, researchers, and a deaf woman eager explaining why she's hopeful for a cure.

Cell, May 14, 2010
CIRM Funding: Stefan Heller (RC1-00119-1)

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NIH accepts new human embryonic stem cell lines

By Geoff Lomax

The NIH has accepted three new human embryonic stem cell lines, created by CIRM grantee Amander Clark at UCLA. According to the UCLA press release:

“The addition of the three human embryonic stem cells lines to the registry brings the total number of lines available for federal funding to 64, NIH officials said. Another 100 lines are pending approval. UCLA is one of only nine institutions in the world with stem cell lines admitted to the NIH registry.”

All lines were created from blastocysts left over from IVF treatments and would otherwise have been discarded. (You can read more about how the lines are created in this CIRM Stem Cell Basics page.)

In this video, Clark describes the process of creating new lines:


It is reassuring to know that the standards CIRM developed in 2006 for hESC derivation are acceptable in the rigorous NIH policy context. This approval is important because it signals that our grantees are well positioned to support research nationally by registering cell lines derived with CIRM funding.

Geoff Lomax is Senior Officer to the CIRM Standards Working Group, which developed CIRM’s stem cell derivation regulations.

Questions About iPS Cells

In his blog, CIRM grantee Paul Knoepfler at UC Davis posted a response to the journal Stem Cells, which had published a list of the most pressing questions about iPS cells:

“What I found most striking is that not one of their 10 questions had anything to do with safety or tumorigenicity, the question I rank #1, but otherwise my top 5 most important questions about IPS cells are similar to theirs. I know they think safety is a crucial issue, which is why I'm so surprised it wasn't on their list.”

Knoepfler's focus on tumorigenicity stems from his lab's work, which he discusses in this video about the safety of stem cell-based therapies (embryonic or iPS).



Knoepfler is taking suggestions for additional top 5 lists.

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Protein Aids Bone Healing

At the intersection of stem cell research and the world of Harry Potter you'll find new work by CIRM grantees at Stanford University School of Medicine that can speed the rate of bone healing by three times. It's not quite Skele-gro, but it's close, at least in mice.

The research is based on a protein called Wnt that was long-known to be involved in the growth of many kinds of tissues and in the differentiation of stem cells. What's new is that the researchers managed to package the Wnt in a form that allows it to be delivered directly to tissues that need it. In a press release, senior author Jill Helms said:

“We believe our strategy has the therapeutic potential to accelerate and improve tissue healing in a variety of contexts.”

Helms and her collaborators delivered the packaged Wnt into the bones of mice with an induced injury. After 28 days, those mice had completely healed while the bones of their untreated lab-mates were still in the repair process. It appears that the Wnt triggers progenitor cells in the bone to multiply and heal the wound. Helms thinks the approach could be useful for healing tissues in addition to bone:

“After stroke and heart attack we heal the injuries slowly and imperfectly, and the resulting scar tissue lacks functionality. Using Wnt may one day allow us to regenerate tissue without scarring.”

From Stanford's blog Scope:

NatureNews also reported on the study, which appears in the journal Science Translational Medicine, and quoted a Columbia University expert who called the work "a major technological advance." But developmental biologist Roel Nusse, PhD, stressed there is still a lot of work to do.

This research marks the 500th paper published with CIRM funding.

Science Translational Medicine, April 28, 2010
CIRM funding: TR1-01249

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