Scar-forming cells in the heart converted directly into beating heart muscle

Last year, our grantees at Gladstone Institutes worked a neat trick: they converted the scar-forming cells of the heart directly into beating heart cells in living mice. (We wrote about that work here.)

The cells they converted, also called fibroblasts, are the ones that create scar tissue in the heart after a heart attack. Their work created the possibility of directly replacing scar tissue with healthy heart muscle following a heart attack.

But that work was in mice. The real test was to work the same conversion in human tissue, which they just published in the journal Stem Cell Reports. The group, which includes senior author Deepak Srivastava and Benoit Bruneau, coerced human fibroblasts in the lab dish to convert directly to beating heart tissue.

A press release from the Gladstone Institutes quotes Srivastava:

“With more than five million heart attack survivors in the United States and climbing each year, our findings come at a critical time. We’ve now laid a solid foundation for developing a way to reverse the damage—something previously thought impossible—and changing the way that doctors may treat heart attacks in the future.”

The group did run into hurdles along the way. They’d originally used a group of three factors to convert the mice fibroblasts to heart muscle. Those same three factors weren’t effective in human cells. Instead, they had to start over, testing a large pool of different factors before narrowing down the group of factors needed to work the conversion. They still have some work to do, too. Only about 20% of the cells converted. Gladstone quotes the lead author Ji-dong Fu talking about this effect:

“Clearly, there are some yet-to-be-determined barriers preventing a more complete transformation for many of the cells. For example, success rates might be improved by transforming the fibroblasts within living hearts rather than in a dish—something we also observed during our initial experiments in mice.”

Gladstone produced this cool 3-D animation about the work:

3D reconstruction of a cardiomyocyte (heart muscle cell), derived from a fibroblast via direct reprogramming. Direct reprogramming allows scientists to transform one cell type into another without first reverting back to the pluripotent, stem-cell state. [Animation: Scott Metzler]

CIRM funding: Deepak Srivastava (RB3-05174); Benoit Bruneau (RN2-00903); Paul Delgado-Olguin (TG2-01160)

Amy Adams

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