Fluorescent hiPSC-derived MYH6-mScarlet cardiomyocytes for real-time tracking, imaging, and cardiotoxicity assays.
2D/3D cardiotoxicity testing
Biomaterial tracking and cytocompatibility tool
Cardiac reporter
Drug toxicity screening
Journal
Cell biology and toxicology
ISSN: 1573-6822
Titre abrégé: Cell Biol Toxicol
Pays: Switzerland
ID NLM: 8506639
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
08
04
2022
accepted:
29
06
2022
medline:
29
3
2023
pubmed:
24
7
2022
entrez:
23
7
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35870039
doi: 10.1007/s10565-022-09742-0
pii: 10.1007/s10565-022-09742-0
pmc: PMC10042918
doi:
Substances chimiques
MYH6 protein, human
0
Myosin Heavy Chains
EC 3.6.4.1
Cardiac Myosins
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
145-163Informations de copyright
© 2022. The Author(s).
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