Abstract
Recent advances in the differentiation and production of human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) have stimulated development of strategies to use these cells in human cardiac regenerative therapies. A prerequisite for clinical trials and translational implementation of hPSC-derived CMs is the ability to manufacture safe and potent cells on the scale needed to replace cells lost during heart disease. Current differentiation protocols generate fetal-like CMs that exhibit proarrhythmogenic potential. Sufficient maturation of these hPSC-derived CMs has yet to be achieved to allow these cells to be used as a regenerative medicine therapy. Insights into the native cardiac environment during heart development may enable engineering of strategies that guide hPSC-derived CMs to mature. Specifically, considerations must be made in regard to developing methods to incorporate the native intercellular interactions and biomechanical cues into hPSC-derived CM production that are conducive to scale-up.
Highlights
Recent advances in the differentiation and production of human pluripotent stem cell-derived cardiomyocytes (CMs) have stimulated development of strategies to use these cells in human cardiac regenerative therapies
With
Standards need to be defined to both quantify the extent of maturation and determine the level of maturation that is optimal for transplantation
Summary
Recent advances in the differentiation and production of human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) have stimulated development of strategies to use these cells in human cardiac regenerative therapies. The epicardial cells, cells that comprise the outer layer of the heart, undergo epithelialto-mesenchymal transition both during heart development and repair to produce SMCs, fibroblasts, and possibly ECs [6, 7]. These SMCs, fibroblasts, and ECs interact with CMs in the myocardium to influence their survival and function. On the other hand, reprogramming fibroblasts is a relatively new and still inefficient method, requiring further characterization of the resulting CMs to determine their subtype and maturity [15] For these reasons, most research has focused on using hPSC-derived CMs to replace native CMs cells lost in cardiac diseases
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