From bedside to the bench: patient-specific hiPSC-EC models uncover endothelial dysfunction in genetic cardiomyopathies

Frontiers in Physiology

Physiology

Serena Zacchigna¹  Martina Rabino²  Elena Sommariva²  Giulio Pompilio³ 

[1] Unit of Cardio-Oncology, Centro Cardiologico Monzino—IRCCS, Milan, Italy;Cardiovascular Biology Laboratory, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy;Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy;Unit of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino—IRCCS, Milan, Italy;Unit of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino—IRCCS, Milan, Italy;Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy;

关键词: human induced pluripotent stem cells (hiPSCs);    hiPSC-derived endothelial cells (hiPSC-ECs);    endothelial dysfunction (ED);    genetic cardiomyopathies;    disease modelling;    personalized medicine;   

DOI  :  10.3389/fphys.2023.1237101

 received in 2023-06-08, accepted in 2023-07-07,  发布年份 2023

来源: Frontiers

【 摘 要 】

Genetic cardiomyopathies are a group of inherited disorders in which myocardial structure and function are damaged. Many of these pathologies are rare and present with heterogenous phenotypes, thus personalized models are required to completely uncover their pathological mechanisms and develop valuable therapeutic strategies. Both cardiomyocytes and fibroblasts, differentiated from patient-specific human induced pluripotent stem cells, represent the most studied human cardiac cell models in the context of genetic cardiomyopathies. While endothelial dysfunction has been recognized as a possible pathogenetic mechanism, human induced pluripotent stem cell-derived endothelial cells are less studied, despite they constitute a suitable model to specifically dissect the role of the dysfunctional endothelium in the development and progression of these pathologies. In this review, we summarize the main studies in which human induced pluripotent stem cell-derived endothelial cells are used to investigate endothelial dysfunction in genetic-based cardiomyopathies to highlight new potential targets exploitable for therapeutic intervention, and we discuss novel perspectives that encourage research in this direction.

【 授权许可】

Unknown   
Copyright © 2023 Rabino, Sommariva, Zacchigna and Pompilio.