Concise Review: The Current State of Human In Vitro Cardiac Disease Modeling: A Focus on Gene Editing and Tissue Engineering

摘要

Until recently, in vivo and ex vivo experiments were the only means to determine factors andpathways involved in disease pathophysiology. After the generation of characterized human embryonicstem cell lines, human diseases could readily be studied in an extensively controllable setting.The introduction of human-induced pluripotent stem cells, a decade ago, allowed the investigationof hereditary diseases in vitro. In the field of cardiology, diseases linked to known genes have successfullybeen studied, revealing novel disease mechanisms. The direct effects of various mutationsleading to hypertrophic cardiomyopathy, dilated cardiomyopathy, arrythmogenic cardiomyopathy,or left ventricular noncompaction cardiomyopathy are discovered as a result of in vitro diseasemodeling. Researchers are currently applying more advanced techniques to unravel more complexphenotypes, resulting in state-of-the-art models that better mimic in vivo physiology. The continuedimprovement of tissue engineering techniques and new insights into epigenetics resulted inmore reliable and feasible platforms for disease modeling and the development of novel therapeuticstrategies. The introduction of CRISPR-Cas9 gene editing granted the ability to model diseasesin vitro independent of induced pluripotent stem cells. In addition to highlighting recent developmentsin the field of human in vitro cardiomyopathy modeling, this review also aims to emphasizelimitations that remain to be addressed; including residual somatic epigenetic signatures inducedpluripotent stem cells, and modeling diseases with unknown genetic causes.