Cardiac regeneration by two approaches: cell transplantation and in-situ reprogramming. (A) Cell transplantation. Top, pluripotent cells are generated either from reprogramming fibroblasts with four factors delivered by retroviral vector (iPSCs), or by extracting inner mass cells from blastocysts (ESCs); and cardiomyocytes are generated by differentiation. Alternatively, cardiac fibroblasts can be directly converted to cardiomyocyte-like cells by retroviral delivery of three genes for cardiac regulators. These cultured cardiomyocytes can be transplanted in or near heart infarcts. (B) In-situ reprogramming. Carried on a retroviral vector, cardiac regulator genes are delivered in vivo, directly to cardiac tissue surrounding infarct, where resident cardiac fibroblasts are converted to cardiomyocytes, reducing the size of infarct from original size (white dotted line).