Methods Toward Maturation of Human Pluripotent Stem Cell-derived Cardiomyocytes for In Vitro and In Vivo Biomedical Applications

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Sara Pahlavan

Royan Institute for Stem Cell Biology and Technology

Sara Pahlavan is an electrophysiologist and a member of Cardiovascular Group at Royan Institute for Stem Cell Biology and Technology. She studied biology in her undergraduate degree and obtained a master degree in physiology from Shiraz University, Iran. For her postgraduate studies, she moved to Germany and joined Prof. Peter Lipp's lab where she learned state-of-the art simultaneous patch clamp and Ca imaging. There, she studied excitation-contraction coupling in cardiomyocytes isolated from healthy as well as transgenic Gq/G11 knockout mice. Doing her postdoctoral fellowship in Prof. Martin Morad's lab at Medical University of South Carolina, she gained insight on in vitro cardiac disease models using human pluripotent stem cells (hPSC)-derived cardiomyocytes. She used simultaneous total internal fluorescent microscopy (TIRF) and patch clamp to study Ca release from ryanodine receptors of sarcoplasmic reticulum. Using hPSC for in vitro disease modeling as well as advanced microscopy, she could mechanistically study the cellular phenotype of some cardiac congenital diseases. She joined Royan Institute for Stem Cell Biology and Technology in 2015 and started a faculty position as assistant professor in cardiovascular group since 2017. Her group is working on generation of in vitro vascularized human cardiac microtissues to establish a preclinical model for mechanistic studies of cardiovascular diseases and drug testing as well as cardiotoxicity in platforms as close to human heart as possible. They are also interested in strategies to improve maturation of in vitro generated hPSC-derived cardiomyocytes. And last but not least, cell-based or cell products-based therapy of cardiac ischemic disease are investigated in preclinical models in her group.

Collection Overview

Most cell types of human organs can be produced by in vitro differentiation of pluripotent stem cells (PSCs). Cardiomyocytes (CM) are among those cells for which in vitro differentiation protocols have been identified. However, most differentiation protocols result in the generation of CM that show the molecular, biochemical, and functional properties of embryonic or fetal cardiac cells rather than adult CM; this restricts their use for disease modeling, drug testing, cardiotoxicity assays, or cell therapy. Various strategies—such as tissue engineering, genetic engineering, and microRNA transfection, in addition to in vitro manipulation of excitation-contraction coupling machinery, prolonged culture, electromechanical stimulation, chemical interventions, or combinations of two or three approaches—have been proposed to overcome this restriction. In this methods collection, the aim is to present recent methodological advancements for the improvement of CM maturation and their outcomes.