oa Cardiomyocyte derivation from human embryonic stem cell derived mesenchymal progenitors

Myocardial infarction or failure is a leading cause of mortality in civilized countries. The cardiomyocytes do not have a high regenerative potential often leading, upon disease progression, to regional contractile dysfunction, and necrotized regions slowly replaced by fibroblasts forming scar tissues. Human embryonic stem cells (hESC) are one of the most promising cell types for cell therapy and tissue engineering or trauma repair. They also represent a model of choice for cell banking. These cells have been differentiated in many different progenitors including: endothelial, hematopoietic, cardiac, hepatocyte, pancreatic, neural and mesenchymal progenitors (MP). One of the major limitations of regenerative medicine is access to a high number of characterized differentiated cells. Therefore, optimizing the differentiation process is a critical step toward clinical application. Stage-specific differentiation protocols relying on subtil cytokine cocktails have allowed derivation of cardiomyocyte progenitors. The use of MPs as precursor cells to derive cardiomyocytes have already been demonstrated in mice, and more recently in human cell lines. We will describe a two step protocol allowing the differentiation of hES-derived MPs and subsequently the differentiation of cardimyocyte like cells.