Learn from Your Elders: Developmental Biology Lessons to Guide Maturation of Stem Cell-Derived Cardiomyocytes

Pediatric Cardiology
Silvia MarchianòCharles E Murry

Abstract

Human pluripotent stem cells (hPSCs) offer a multifaceted platform to study cardiac developmental biology, understand disease mechanisms, and develop novel therapies. Remarkable progress over the last two decades has led to methods to obtain highly pure hPSC-derived cardiomyocytes (hPSC-CMs) with reasonable ease and scalability. Nevertheless, a major bottleneck for the translational application of hPSC-CMs is their immature phenotype, resembling that of early fetal cardiomyocytes. Overall, bona fide maturation of hPSC-CMs represents one of the most significant goals facing the field today. Developmental biology studies have been pivotal in understanding the mechanisms to differentiate hPSC-CMs. Similarly, evaluation of developmental cues such as electrical and mechanical activities or neurohormonal and metabolic stimulations revealed the importance of these pathways in cardiomyocyte physiological maturation. Those signals cooperate and dictate the size and the performance of the developing heart. Likewise, this orchestra of stimuli is important in promoting hPSC-CM maturation, as demonstrated by current in vitro maturation approaches. Different shades of adult-like phenotype are achieved by prolonging the time in culture, elect...Continue Reading

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Citations

Feb 6, 2020·Nature Reviews. Cardiology·Elaheh KarbassiCharles E Murry
Nov 25, 2020·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Rui ZhangFeng Lan
Feb 13, 2021·Developmental Biology·Haruko NakanoAtsushi Nakano
Mar 19, 2021·Frontiers in Genetics·Alessandro Bertero
Mar 30, 2021·Seminars in Cell & Developmental Biology·Matthew MiyamotoChulan Kwon
Feb 20, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Willem J de LangeJ Carter Ralphe
May 20, 2021·Advanced Biology·Naimeh RafatianMilica Radisic

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