The heart contains a relatively large amount of tissue that does not participate in the process of pumping blood. Researchers have speculated that this tissue could be tapped to replace damaged muscle following a heart attack or other heart trauma.
Investigators at the University of California, San Francisco (USA) had previously shown that differentiated heart fibroblasts could be "deprogrammed” into a type of pluripotent stem cell. Now, in a study published in the August 6, 2010, issue of the journal Cell they described transforming cardiac dermal fibroblasts directly into functioning cardiomyocytes without first reverting to a pluripotent stem cell stage.
The transformation was prompted by the combined action of three transcription factors, Gata4, Mef2c, and Tbx5. Cardiomyocytes induced by the action of these factors expressed cardiac-specific markers, had a global gene expression profile similar to normal cardiomyocytes, and contracted spontaneously. Fibroblasts transplanted into mouse hearts one day after transduction of the three factors also differentiated into cardiomyocyte-like cells.
The authors concluded by saying, "We believe these findings demonstrate that functional cardiomyocytes can be directly reprogrammed from differentiated somatic cells by defined factors. Reprogramming of endogenous or explanted fibroblasts might provide a source of cardiomyocytes for regenerative approaches.”
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