Tracking stem cells using tricks learned in outer space

Stem cell science is set to get a boost from an unlikely source: outer space. It turns out that techniques devised to help telescopes peer through the blur of the earth's atmosphere could help scientists peak more deeply into tissues. If the technique, called adaptive optics or AO, works it might prove useful for scientists hoping to track the whereabouts of transplanted stem cells.

A group of researchers at the University of California, Santa Cruz, including CIRM grantee Joel Kubby, have formed the W. M. Keck Center for Adaptive Optical Microscopy, which will apply AO techniques to microscopes built for peering deep into tissues.

A press release from UCSC describes the project:

Principal investigator Joel Kubby, an associate professor of electrical engineering in the Baskin School of Engineering at UCSC, has worked on adaptive optics (AO) systems for large telescopes as well as for biological imaging. In astronomy, AO systems correct the blurring of telescope images caused by turbulence in the Earth's atmosphere. In microscopy, blurring is caused by the flowing cytoplasm of living cells.

"We can get beautiful images of cells close to the surface of the tissue, but if you want to go deep you're out of luck because of the degradation of the image. That was the motivation for this project," said co-investigator William Sullivan, professor of molecular, cell, and developmental biology at UC Santa Cruz. "For cell biologists, anything that improves imaging is a big deal, and this has the potential to open up vast areas of cell biology that have been opaque to us."

In stem cell research, for example, an important bottleneck in efforts to develop stem cell therapies has been the inability to follow injected stem cells and monitor their fates below the surface of the tissue. AO microscopy could solve this problem, and the California Institute for Regenerative Medicine (CIRM) has provided support for the work at UCSC, including funding that led to the development of the team's first AO microscope.

Knowing where a stem cell goes once it has been transplanted is critical to developing new therapies. Unless they go to where the damage is and stay there, those cells won't hold any long-term therapeutic benefit. Tracking cells within tissues could point to better ways of transplanting the cells and, eventually, to more effective therapies.

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Muscle stem cells a step closer to treating muscular dystrophy

Stanford scientists have overcome one significant hurdle in developing a therapy for muscle-wasting diseases like muscular dystrophy. Until now, the muscle stem cells that stand at the ready to repair muscle damage couldn’t be grown outside the safe confines of a muscle. Once uprooted from their home and transferred to a laboratory dish, they matured into less useful progenitor cells. That’s a problem because once mature the cells no longer have the potential to be transplanted to repair muscle damaged by injury or disease.

Until Helen Blau, CIRM grantee and Stanford”s Donald E. and Delia B. Baxter Professor, had a good idea, that is. According to a Stanford press release:

The researchers wondered if the way the cells are normally grown in culture could be the problem. After all, as Blau pointed out, cells are used to rubbing shoulders comfortably with their neighbors on all sides rather than being splayed out and anchored on a rigid plastic culture dish that is 100,000-fold less elastic than true muscle.

Blau and her team grew the cells on a hydrogel that mimicked the elasticity of muscle, and voila. In the Stanford press release Blau said:

“Clearly the cells grown on the more-elastic surfaces have better survival and self-renewing properties than those grown on standard tissue culture dishes. We conducted our experiments with muscle stem cells, but I expect this will be true for other types of adult stem cells as well.”

When transplanted into mice, the cells contributed to leg muscles, showing that the cells were not only more numerous but also therapeutically useful. The group said this discovery could pave the way for scientists to grow muscle stem cells in quantities needed for transplantation therapies to treat muscular dystrophy and other muscle diseases.

Science (Express Online) July 15, 2010
CIRM funding: PM Gilbert (TG2-01159); Helen Blau (RT1-01001)

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Small DNA changes, life or death consequences

Two recent papers by CIRM grantees highlight the importance of understanding basic stem cell biology while developing new cures. Both have to do with chemical modifications to the DNA – called epigenetics.

One of the two papers shows that an epigenetic change in DNA, called methylation, changes dramatically as human embryonic stem cells mature into specific cell types; the other shows that even subtle DNA methylation differences alter the way a cell behaves.

The first paper, by Jeanne Loring at The Scripps Research Institute, working with scientists in Singapore and New York, provides detailed maps of DNA methylation over the entire 3 billion “letters” that make up our DNA. By comparing methylation patterns of human embryonic stem cells and more mature cells, the scientists tracked the large number of epigenetic changes, many of them surprises, that occur when cells differentiate.

A press release quotes first author Louise Laurent as saying:

"The data are publicly available, and we are looking forward to learning what other scientists discover from using this information for their own studies on individual genes, embryonic development, and stem cells."

The second paper, from UCLA, focuses on epigenetic differences in pancreatic cancers, showing that differences in these modifications translate to different responses to chemotherapy. This means that a few DNA modifications here or there could mean life or death.

In a press release the authors say the next step is to develop a test doctors can use to figure out which patients will respond well to standard chemotherapy and which need an alternative treatment.

Taken together, the papers make a compelling case for how basic biology research such as understand DNA modifications can inform scientists who are actively pursuing cures.

Genome Research, February 4, 2010
CIRM funding: Jeanne Loring (RT1-1108 and TR1-01250)

Journal of Clinical Oncology, February 8, 2010
CIRM funding: Siavash Kurdistani (RN1-005505)

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