Drug Discovery Opinion

Once damaged, heart muscle has very limited capacity for regeneration but scientists at the Gladstone Institute of Cardiovascular Diseases have now discovered how to reprogram structural fibroblasts into functioning cardiac muscle cells (cardiomyocytes). The team explored the effects of transcription factors known to be important for development of the heart and found that a combination of just three (Gata4, Mef2c and Tbx5) was sufficient to rapidly and efficiently convert cardiac or dermal fibroblasts into contractile cardiomyocyte-like cells.

Gladstone scientists have previously converted mouse mesoderm – germ tissue from very early embryos – into cardiomyocytes and have reprogrammed adult cells into induced pluripotent cells which can then be converted into other cell types but, in the present study, adult cells have been directly reprogrammed into a different type of cell without involvement of a progenitor cell state. The team hope that going directly from one adult cell type to another might eliminate some of the perceived risks associated with the use of stem cells and that it will be possible to identify small molecules that are able to trigger the conversion. Although the technique has yet to be tested in human cells, and further refinement and characterisation of the reprogramming process will be needed, the heart has a large pool of fibroblasts which provide a potential source for regenerative treatments if they could be directly reprogrammed to beating cardiomyocytes.

The study is published in the journal Cell.

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