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barbara
02-09-2010, 07:10 PM
By Victoria Stern, "The Scientist"
Reviving hearts

The paper:
M. Laflamme et al., ?Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts,? Nat Biotech, 25:993?94, 2007. (Cited in 140 papers)

The finding:
Charles Murry and his colleagues at the University of Washington demonstrated that cardiomyocytes derived from human embryonic stem cells (hESCs) can help repair an infarcted rat heart. Murry?s team developed a novel protocol to guide all the hESCs to differentiate into cardiomyocytes, then exposed the cells to a prosurvival cocktail (PSC). ?Our method worked 50-fold better than previous efforts at forming cardiac muscle,? says Murry. Ten percent of these cardiomyocytes survived, where none had survived in previous experiments.

The impact:
?This is the first study to demonstrate improved function following an infarct,? Dan Rodgers, a molecular biologist at the University of California, Berkeley, writes in an email.

The details:
To ensure hESCs differentiated into mature cardiomyocytes, the team treated the cells with two proteins (activin A and BMP4) that promote cell differentiation. The PSC consisted of six key ingredients, including use of a hydrogel called Matrigel and enhanced activity of a caspase inhibitor to prevent apoptosis.

The future:
The team recently started working on strengthening the approaches they?ve established with the PSC technique, such as creating better hydrogel agents to support cell survival.
The PSC:
1. Increased function of a Bcl-XL to block cell death.
2. Administered the immunosuppressant drug cyclosporine A.
3. Enhanced insulin-like growth factor 1 (IGF-1) activity to activate Akt pathways, thus inhibiting apoptotic processes.
4. Included the drug pinacidil to open ATP-dependent K+ channels, protecting tissues from ischemia.