Human myofibroblasts increase the arrhythmogenic potential of human induced pluripotent stem cell-derived cardiomyocytes.

ABSTRACT: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have the potential to remuscularize infarcted hearts but their arrhythmogenicity remains an obstacle to safe transplantation. Myofibroblasts are the predominant cell-type in the infarcted myocardium but their impact on transplanted hiPSC-CMs remains poorly defined. Here, we investigate the effect of myofibroblasts on hiPSC-CMs electrophysiology and Ca²⁺ handling using optical mapping of advanced human cell coculture systems mimicking cell-cell interaction modalities. Human myofibroblasts altered the electrophysiology and Ca²⁺ handling of hiPSC-CMs and downregulated mRNAs encoding voltage channels (K_V4.3, K_V11.1 and Kir6.2) and SERCA2a calcium pump. Interleukin-6 was elevated i

SUBMITTER: Johnson RD 

PROVIDER: S-EPMC10480244 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature