Efficient differentiation of cardiomyocytes and generation of calcium-sensor reporter lines from nonhuman primate iPSCs View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Yongshun Lin, Huimin Liu, Michael Klein, John Ostrominski, So Gun Hong, Ravi Chandra Yada, Guibin Chen, Keron Navarengom, Robin Schwartzbeck, Hong San, Zu-Xi Yu, Chengyu Liu, Kaari Linask, Jeanette Beers, Lugui Qiu, Cynthia E. Dunbar, Manfred Boehm, Jizhong Zou

ABSTRACT

Nonhuman primate (NHP) models are more predictive than rodent models for developing induced pluripotent stem cell (iPSC)-based cell therapy, but robust and reproducible NHP iPSC-cardiomyocyte differentiation protocols are lacking for cardiomyopathies research. We developed a method to differentiate integration-free rhesus macaque iPSCs (RhiPSCs) into cardiomyocytes with >85% purity in 10 days, using fully chemically defined conditions. To enable visualization of intracellular calcium flux in beating cardiomyocytes, we used CRISPR/Cas9 to stably knock-in genetically encoded calcium indicators at the rhesus AAVS1 safe harbor locus. Rhesus cardiomyocytes derived by our stepwise differentiation method express signature cardiac markers and show normal electrochemical coupling. They are responsive to cardiorelevant drugs and can be successfully engrafted in a mouse myocardial infarction model. Our approach provides a powerful tool for generation of NHP iPSC-derived cardiomyocytes amenable to utilization in basic research and preclinical studies, including in vivo tissue regeneration models and drug screening. More... »

PAGES

5907

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-018-24074-y

    DOI

    http://dx.doi.org/10.1038/s41598-018-24074-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1103231895

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29651156


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