Year 2

Cardiomyocyte-like cells can be reprogrammed from somatic fibroblasts by combinations of genes in vitro1 and in vivo, providing a new avenue for cardiac regenerative therapy. However, transdifferentiating human cells to generate fully functional cardiomyocytes remains a challenge. Moreover, genetic manipulations with multiple factors used in such conventional strategies pose safety, efficacy, and technical concerns that may limit their clinical potential. In the work funded by CIRM we identified and demonstrated that functional cardiomyocytes can be rapidly and efficiently generated from fibroblasts by a combination of small molecules. These cardiomyocytes express characteristic cardiac markers, have a well-organized sarcomeric structure, contract spontaneously, and respond to pharmacological modulations. They closely resemble cardiomyocytes in their global gene expression profiles, and electrophysiological properties. This novel pharmacological reprogramming approach may have important implications in cardiac regenerative medicine.