News Release

Nine chemical compounds induced fibroblasts to act as cardiac cells

Peer-Reviewed Publication

American Association for the Advancement of Science (AAAS)

Researchers have induced human fibroblasts into cardiomyocyte-like cells using just nine compounds, and show that these modified cells can be used to partially heal mouse hearts following a heart attack. Cardiomyocytes are muscle cells in the heart that help it beat, but these can become damaged following heart attack. Inducing non-cardiac cells to act as cardiomyocytes and transferring them to the heart could open new avenues for cardiac regenerative therapies, similar to how stem cells have contributed to regenerative medicine. Genetically manipulating non-cardiac cells is one option, but this has yielded only a marginal percentage of cells with clear cardiomyocyte-like qualities to date. As well, there are several advantages to using small molecules over genetic manipulation; for example, such compounds can efficiently be delivered into a cell, will not evoke an immune response, and are more cost-effective than genetic manipulation. Most importantly, these compounds do not introduce genetic material that might create unwanted mutation or trigger uncontrolled cell growth. To identify compounds that may induce cardiomyocyte-like features, Nan Cao et al. screened a collection of 89 small molecules known to facilitate cell reprogramming. Applying various cocktails of the compounds to human foreskin fibroblast (HFF) cells revealed a core 15 compounds that could induce cardiomyocyte-like qualities. Further elimination of which compounds were not essential led to the identification of seven compounds that gave the cells "beating" properties. Two additional compounds that accelerated the down-regulation of fibroblast genes and increased the yield of beating clusters were also identified. This nine-compound (9C) cocktail induced cardiomyocyte-like qualities in roughly 27% of HFF cells. In contrast, previous efforts using genetic manipulation have yielded cardiomyocyte-like qualities in 0.1% of non-cardiac cells. The researchers then applied 9C-treated HHFs into the hearts of mice after a heart attack, finding that this helped partially re-muscularized damaged areas two weeks after transplantation.

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