Scar tissue transformed into beating cells in the hearts of mice

Heart muscle cells directly reprogrammed from skin, Deepak Srivastava, Gladstone Institutes

CIRM grantees at the Gladstone Institutes in San Francisco have carried out a remarkable feat: They directly converted scar-forming cells in the mouse heart into beating cells.

We’ve previously blogged about work led by Deepak Srivastava, who had converted non-beating heart cells in the lab dish into beating cells. (These non-beating cells are called heart fibroblasts, which make up about half the cells of the heart.) In a press release that accompanied that 2010 publication, Srivastava had speculated that if the same feat could be carried out in the living heart it could represent a way of repairing damage after a heart attack.

Now, he and his team have shown that the same group of molecules that directed the cellular transformation in the lab dish is also effective in living heart tissue, at least in mice. The work appears today in the advanced online publication of Nature.

A press release from the Gladstone Institutes quotes Srivastava, who directs cardiovascular and stem cell research at Gladstone and was senior author on the study. Srivastava is also a professor at the University of California, San Francisco.

“The damage from a heart attack is typically permanent because heart-muscle cells—deprived of oxygen during the attack—die and scar tissue forms. But our experiments in mice are a proof of concept that we can reprogram non-beating cells directly into fully functional, beating heart cells—offering an innovative and less invasive way to restore heart function after a heart attack.”

This work builds directly on a discovery by another Gladstone scientist, Shinya Yamanaka, who in 2006 first showed that adult cells could be reprogrammed to an embryonic-like state. In recent years, researchers have expanded that work to convert adult cells directly into other types of adult cells. This is the first time the technique has been shown to work in a living animal.

As always, it’s important to note that there’s a big difference between mice and humans. Srivastava says the team’s next step is to see if their technique works in other animals before beginning work toward clinical trials in humans. If the work continues to go well, he says:

“We hope that our research will lay the foundation for initiating cardiac repair soon after a heart attack—perhaps even when the patient arrives in the emergency room.”

A.A.

CIRM funding: Li Quan (TG2-01160), Deepak Srivastava (RB3-05174)