Fluorescent hiPSC-derived MYH6-mScarlet cardiomyocytes for real-time tracking, imaging, and cardiotoxicity assays.

Autor: Maria Cherian R; Heart Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. reeja.maria.cherian@tuni.fi., Prajapati C; Heart Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland., Penttinen K; Heart Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland., Häkli M; Heart Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland., Koivisto JT; Biomaterials and Tissue Engineering Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden., Pekkanen-Mattila M; Heart Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland., Aalto-Setälä K; Heart Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. katriina.aalto-setala@tuni.fi.; Heart Hospital, Tampere University Hospital, Tampere, Finland. katriina.aalto-setala@tuni.fi.
Jazyk: angličtina
Zdroj: Cell biology and toxicology [Cell Biol Toxicol] 2023 Feb; Vol. 39 (1), pp. 145-163. Date of Electronic Publication: 2022 Jul 23.
DOI: 10.1007/s10565-022-09742-0
Abstrakt: Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) hold great potential in the cardiovascular field for human disease modeling, drug development, and regenerative medicine. However, multiple hurdles still exist for the effective utilization of hiPSC-CMs as a human-based experimental platform that can be an alternative to the current animal models. To further expand their potential as a research tool and bridge the translational gap, we have generated a cardiac-specific hiPSC reporter line that differentiates into fluorescent CMs using CRISPR-Cas9 genome editing technology. The CMs illuminated with the mScarlet fluorescence enable their non-invasive continuous tracking and functional cellular phenotyping, offering a real-time 2D/3D imaging platform. Utilizing the reporter CMs, we developed an imaging-based cardiotoxicity screening system that can monitor distinct drug-induced structural toxicity and CM viability in real time. The reporter fluorescence enabled visualization of sarcomeric disarray and displayed a drug dose-dependent decrease in its fluorescence. The study also has demonstrated the reporter CMs as a biomaterial cytocompatibility analysis tool that can monitor dynamic cell behavior and maturity of hiPSC-CMs cultured in various biomaterial scaffolds. This versatile cardiac imaging tool that enables real time tracking and high-resolution imaging of CMs has significant potential in disease modeling, drug screening, and toxicology testing.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz: