Researchers Transform Non-beating Human Cells into Heart-Muscle Cells

Researchers have found a way to transform the class of cells that form scar tissue into those closely resembling beating heart cells, a discovery that places scientists a significant step closer to healing a heart's cells in the aftermath of a heart attack.

This same group of scientists last year transformed scar-forming heart cells, which belong to a class of cells known as fibroblasts, into beating heart-muscle cells in live mice. In a new study published in the journal Stem Cell Reports, the team show how they have been able to take this research one step further by doing the same to human cells in a petri dish.

According to co-author Dr. Deepak Srivastava, the researchers were able to reprogram fibroblasts into beating heart cells in mice by injecting three genes, and hypothesized that the same could be true for human cells.

However, further research showed this was not the case, and the team of scientists were forced back to the drawing board in order to identify further genes needed to help carry out the process.

Eventually, they narrowed their search down to just 16 genes in addition to the original three and began injecting all the candidates into the human fibroblasts, systematically removing them one at a time in order to determine those alone necessary for reprogramming.

The group ended up with a cocktail of five genes that proved sufficient in carrying out the process, and two others that, when added, helped to further complete the transformation.

Finally, the researchers used a chemical reaction known as TGF-ß signaling pathway during the early stages of reporgramming that improved success rates.

"While almost all the cells in our study exhibited at least a partial transformation, about 20 percent of them were capable of transmitting electrical signals-a key feature of beating heart cells," explained Gladstone Staff Scientist and the study's lead author Dr. Ji-dong Fu. "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."

Going forward, the researchers plan on testing the five-gene cocktail in the hearts of larger mammals with the hopes of one day replacing it with a combination of small, drug-like molecules -- a step that would ensure safer and easier delivery.

"With more than five million heart attack survivors in the United States, who have hearts that are no longer able to beat at full capacity, our findings -- along with recently published findings from our colleagues -- come at a critical time," Srivastava said. "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."