Early first trimester human embryonic cardiac Islet-1 progenitor cells and cardiomyocytes: Immunohistochemical and electrophysiological characterization

The aims of this study were to systematically characterize the distribution, proliferation, and differentiation of Islet-1⁺(Isl1⁺) progenitor cells in the early first trimester human embryonic heart during which period most of the organogenesis takes place. In hearts of gestational week 5 to 10 Isl1⁺cells were identified and mainly clustered in the outflow tract and to a lesser extent in the atria and in the right ventricle. Some of the clusters were also troponin T⁺. Unexpectedly a only few Isl1⁺cells were Ki67⁺while in the ventricles a majority of Isl1^?troponinT⁺cells were Ki67⁺. Cultures derived from the digested embryonic heart developed into spontaneously beating cardiospheres. At harvest cells in these cardiospheres showed frequent expression of troponin T⁺and Nkx2.5⁺, while Isl1 was expressed only in scattered cells. Only a minority of the cultured cells expressed Ki67. The cardiospheres could be frozen, thawed, and recultured to beating cardiospheres. In a multielectrode array system, the beating cardiospheres were responsive to adrenergic stimulation and exhibited rate-dependent action potential duration. In conclusion, the early first trimester human embryonic heart expresses clusters of Isl1⁺cells, some of which differentiate into cardiomyocytes. Unexpectedly, only a minority of the Isl1⁺cells, while a majority of ventricular cardiomyocytes, were proliferating. Spontaneously beating cardiospheres could be derived from the human embryonic heart and these cardiospheres showed functional frequency control.