Myocardial regeneration strategies using human embryonic stem cell-derived cardiomyocytes

Regenerative medicine is a new biomedicine discipline that takes advantage of the recent advancements in the fields of stem cell biology, molecular biology, and tissue engineering to derive tissue substitutes, in an attempt to replace or modify the function of diseased organs. The heart represents an attractive candidate for these emerging technologies since adult cardiac tissue has limited regenerative capacity. Consequentially, myocardial cell replacement therapy has emerged as a novel therapeutic paradigm for restoration of the myocardial electromechanical function. This innovative strategy has been significantly hampered, however, by the paucity of cell sources for human cardiomyocytes. The recent establishment of the human embryonic stem cell (hESC) lines may provide a possible solution for this cell-sourcing problem. These unique pluripotent cell lines can be propagated in the undifferentiated state in culture and coaxed to differentiate into cell derivatives of all three germ layers, including cardiomyocytes. This review will describe the hESC system, their differentiation into cardiomyocytes, and the structural and functional characterization of these cardiac lineage derivatives. The potential applications of this unique differentiating system in several research areas will be discussed with special emphasis on the steps required to fully harness their unique potential in the emerging field of cardiovascular regenerative medicine. (c) 2006 Elsevier B.V. All rights reserved.