Human derived cardiomyocytes: A decade of knowledge after the discovery of induced pluripotent stem cells

Ten years ago Yamanaka's lab identified a way to reprogram terminally differentiated cells to a pluripotent state, similar to that of embryonic stem cell. This procedure opened the road for the generation of postmitotic human cells, that have completely lost the replication potential. The initial excitement waned when it was observed that the cells produced by this method are somehow immature and do not resemble the adult phenotype. In the absence of cellular markers that recognize the various maturation steps of induced pluripotent stem cell-derived human cardiomyocytes, we propose to follow their maturation looking at their electrophysiological profile. For this reason, we are first reviewing the most common methods of differentiation, from the preliminary complex procedures to the newly-identified two-step protocols and, second, we report the electrical characteristics of the cells, through electrophysiological analysis of ionic currents that give rise to the action potential. We are aware that each protocol leads to the generation of different cardiomyocyte precursors, thus suggesting the need for a wider standardization. The identification of the electrophysiological characteristics of the cells could help in identifying the type and the maturation stage of the obtained cardiomyocyte, thus compensating for the lack of specific markers. Developmental Dynamics 245:1145-1158, 2016. (c) 2016 Wiley Periodicals, Inc.