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Abstract
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.
Original language | English |
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Pages (from-to) | 145–163 |
Number of pages | 19 |
Journal | CELL BIOLOGY AND TOXICOLOGY |
Volume | 39 |
Issue number | 1 |
Early online date | 2022 |
DOIs | |
Publication status | Published - 2023 |
Publication type | A1 Journal article-refereed |
Publication forum classification
- Publication forum level 1
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
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Dive into the research topics of 'Fluorescent hiPSC-derived MYH6-mScarlet cardiomyocytes for real-time tracking, imaging, and cardiotoxicity assays'. Together they form a unique fingerprint.Activities
- 1 Conference presentation
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Biomaterials for stem cell-based cardiac disease modelling applications
Koivisto, J. T. (Speaker), Maria Cherian, R. (Contributor), Häkli, M. (Contributor), Parraga Meneses, J. (Contributor), Karvinen, J. (Contributor), Gering, C. (Contributor), Prajapati, C. (Contributor), Pölönen, R.-P. (Contributor), Belay, B. (Contributor), Hyttinen, J. (Contributor), Pekkanen-Mattila, M. (Contributor), Kellomäki, M. (Contributor) & Aalto-Setälä, K. (Contributor)
22 Mar 2023Activity: Talk or presentation › Conference presentation