Journal
STEM CELL REPORTS
Volume 9, Issue 5, Pages 1546-1559Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2017.09.007
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Funding
- Japan Society for the Promotion of Science (JSPS) [15H03948, 26289065, 23310087, 26286027, 15K08270, 26.04046]
- Japan Agency for Medical Research and Development (AMED) program
- European Commission [604263]
- French National Research Agency (ANR) [ANR-12-RPIB-0015]
- World Premier International Research Centre Initiative (WPI), MEXT, Japan
- TERUMO Company
- Grants-in-Aid for Scientific Research [26289065, 15K08270, 15H03948, 26286027] Funding Source: KAKEN
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High-purity cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) are promising for drug development and myocardial regeneration. However, most hiPSC-derived CMs morphologically and functionally resemble immature rather than adult CMs, which could hamper their application. Here, we obtained high-quality cardiac tissue-like constructs (CTLCs) by cultivating hiPSC-CMs on low-thickness aligned nanofibers made of biodegradable poly(D,L-lactic-co-glycolic acid) polymer. We show that multilayered and elongated CMs could be organized at high density along aligned nanofibers in a simple one-step seeding process, resulting in upregulated cardiac biomarkers and enhanced cardiac functions. When used for drug assessment, CTLCs were much more robust than the 2D conventional control. We also demonstrated the potential of CTLCs for modeling engraftments in vitro and treating myocardial infarction in vivo. Thus, we established a handy framework for cardiac tissue engineering, which holds high potential for pharmaceutical and clinical applications.
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