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Differentiation Pathways in Human Embryonic Stem Cell-Derived Cardiomyocytes
SOPHIE LEV,
IZHAK KEHAT AND
LIOR GEPSTEIN
The B. Rappaport Institute in the Medical Sciences, Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
Address for correspondence: Lior Gepstein, M.D, Ph.D. The Shonis Family Research Laboratory for the Regeneration of Functional Myocardium. The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, 2 Efron St., POB 9649, Haifa, 31096, Israel. Voice: 972-4-8295303; fax: 972-4-8524758. mdlior{at}tx.technion.ac.il
Human embryonic stem (hES) cells are pluripotent cell lines derived from the inner cell mass of the blastocyst-stage embryo. These unique cell lines can be propagated in the undifferentiated state in culture, while retaining the capacity to differentiate into derivatives of all three germ layers, including cardiomyocytes. The derivation of the hES cell lines presents a powerful tool to explore the early events of cardiac progenitor cell specification and differentiation, and it also provides a novel cell source for the emerging field of cardiovascular regenerative medicine. A spontaneous differentiation system of these stem cells to cardiomyocytes was established and the generated myocytes displayed molecular, structural, and functional properties of early-stage heart cells. In order to follow the in vitro differentiation process, the temporal expression of signaling molecules and transcription factors governing early cardiac differentiation was examined throughout the process. A characteristic pattern was noted recapitulating the normal in vivo cardiac differentiation scheme observed in other model systems. This review discusses the known pathways involved in cardiac specification and the possible factors that may be used to enhance cardiac differentiation of hES cells, as well as the steps required to fully harness the enormous potential of these unique cells.
Key Words: cardiac differentiation • cell therapy • human embryonic stem cells
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