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)
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.
“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.
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 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.
|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.|