Human Induced Pluripotent Stem Cells as a Disease Model System for Heart Failure
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TRANSLATIONAL RESEARCH IN HEART FAILURE (J BACKS & M VAN DEN HOOGENHOF, SECTION EDITORS)
Human Induced Pluripotent Stem Cells as a Disease Model System for Heart Failure Anton Deicher 1 & Timon Seeger 1,2 Accepted: 4 September 2020 # The Author(s) 2020
Abstract Purpose of Review Heart failure is among the most prevalent disease complexes overall and is associated with high morbidity and mortality. The underlying aetiology is manifold including coronary artery disease, genetic alterations and mutations, viral infections, adverse immune responses, and cardiac toxicity. To date, no specific therapies have been developed despite notable efforts. This can especially be attributed to hurdles in translational research, mainly due to the lack of proficient models of heart failure limited translation of therapeutic approaches from bench to bedside. Recent Findings Human induced pluripotent stem cells (hiPSCs) are rising in popularity, granting the ability to divide infinitely, to hold human, patient-specific genome, and to differentiate into any human cell, including cardiomyocytes (hiPSC-CMs). This brings magnificent promise to cardiological research, providing the possibility to recapitulate cardiac diseases in a dish. Advances in yield, maturity, and in vivo resemblance due to straightforward, low-cost protocols, high-throughput approaches, and complex 3D cultures have made this tool widely applicable. In recent years, hiPSC-CMs have been used to model a wide variety of cardiac diseases, bringing along the possibility to not only elucidate molecular mechanisms but also to test novel therapeutic approaches in the dish. Summary Within the last decade, hiPSC-CMs have been exponentially employed to model heart failure. Constant advancements are aiming at improvements of differentiation protocols, hiPSC-CM maturity, and assays to elucidate molecular mechanisms and cellular functions. However, hiPSC-CMs are remaining relatively immature, and in vitro models can only partially recapitulate the complex interactions in vivo. Nevertheless, hiPSC-CMs have evolved as an essential model system in cardiovascular research. Keywords Heart failure . Human induced pluripotent stem cells . Cardiomyocytes . Disease model
Introduction Cardiovascular diseases remain the number one cause of death worldwide with heart failure being among the leading factors This article is part of the Topical Collection on Translational Research in Heart Failure * Timon Seeger [email protected] 1
Department of Internal Medicine III, University Hospital Heidelberg, INF 410, 69126 Heidelberg, Germany
2
German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Heidelberg, Germany
for morbidity and mortality [1, 2]. However, despite numerous investments and enormous motivation, treatment advances and development of new drugs have been significantly low. Major reasons for the scarcity of novel and specific therapeutic approaches can be contributed to significant weaknesses in adequate model systems for mechanistical
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