Further Developments In the Electrophysiology of Induced Stem-Cell Derived Human Cardiomyocytes

Production of human cardiac cells by genetic reprogramming offers exciting possibilities for tissue repair, artificial organs and the testing of new drugs.  The electrophysiological behavior of the artificial cells is important and must be understood for all of these applications.  This review summarizes the findings of a large number of experimental papers that have appeared in the last ten years.  Recurring themes in this review are the use of tissue culture factors to "program" the specialized differentiation of cardiac cells, the use of adenoviruses to add specific genes to the cardiomyocyte transcriptome, and the ability of transplanted cells to cause favorable and lasting "paracrine effects" even when the transplanted cells to do not permanently survive within the host tissue.  Electrophysiological effects can include up-regulation of ion channels that hyperpolarize the membrane, which reduces beat frequency, or up-regulation of depolarizing ion channels, which increases beat frequency.  Evidence that transplanted myocytes can sometimes align and couple with the host myocytes, and thereby augment contractile force is discussed.  Most of the studies reviewed here involve animal research, although promising clinical studies have already been reported.