Human Cardiac Organoids for Modeling Genetic Cardiomyopathy

• Published in: Cells (Basel, Switzerland) Vol. 9; no. 7; p. 1733
• Main Authors: Filippo Buono, Michele, von Boehmer, Lisa, Strang, Jaan, P. Hoerstrup, Simon, Y. Emmert, Maximilian, Nugraha, Bramasta
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.07.2020; MDPI
• Subjects: 3D culture; Adult; Cardiomyocytes; Cardiomyopathies - genetics; Cardiomyopathies - pathology; Cardiomyopathy; Cell culture; Cell Differentiation; Coronary artery disease; differentiation; Disease; Drug development; Endothelial cells; Fibroblasts; Gene expression; Heart; Heart diseases; hiPSCs; Humans; in vitro disease modeling; Induced Pluripotent Stem Cells - pathology; Microvasculature; Models, Cardiovascular; Mutation; Myocardium; Myocytes, Cardiac - pathology; Organoids; Organoids - pathology; Performance evaluation; Phenotype; Pluripotency; R&D; Research & development; Stem cells; Structure-function relationships; United States > US; Switzerland; cardiomyocytes; in vitro disease modeling; hiPSCs; 3D culture; differentiation; organoids; personalized medicine
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9071733

Genetic cardiomyopathies are characterized by changes in the function and structure of the myocardium. The development of a novel in vitro model could help to better emulate healthy and diseased human heart conditions and may improve the understanding of disease mechanisms. In this study, for the first time, we demonstrated the generation of cardiac organoids using a triculture approach of human induced pluripotent stem-cell-derived cardiomyocytes (hiPS-CMs)—from healthy subjects and cardiomyopathy patients—human cardiac microvascular endothelial cells (HCMECs) and human cardiac fibroblasts (HCFs). We assessed the organoids’ suitability as a 3D cellular model for the representation of phenotypical features of healthy and cardiomyopathic hearts. We observed clear differences in structure and beating behavior between the organoid groups, depending on the type of hiPS-CMs (healthy versus cardiomyopathic) used. Organoids may thus prove a promising tool for the design and testing of patient-specific treatments as well as provide a platform for safer and more efficacious drug development.