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Steps toward maturation of embryonic stem cell-derived cardiomyocytes by defined physical signals

: Shen, Nian; Knopf, Anne; Westendorf, Claas; Kraushaar, Udo; Riedl, Julia; Bauer, Hannah; Pöschel, Simone; Layland, Shannon L.; Holeiter, Monika; Knolle, Stefan; Brauchle, Eva; Nsair, Ali; Hinderer, Svenja; Schenke-Layland, Katja

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Stem cell reports 9 (2017), No.1, pp.122-135
ISSN: 2213-6711
Journal Article, Electronic Publication
Fraunhofer IGB ()

Cardiovascular disease remains a leading cause of mortality and morbidity worldwide. Embryonic stem cell-derived cardiomyocytes (ESC-CMs) may offer significant advances in creating in vitro cardiac tissues for disease modeling, drug testing, and elucidating developmental processes; however, the induction of ESCs to a more adult-like CM phenotype remains challenging. In this study, we developed a bioreactor system to employ pulsatile flow (1.48 mL/min), cyclic strain (5%), and extended culture time to improve the maturation of murine and human ESC-CMs. Dynamically-cultured ESC-CMs showed an increased expression of cardiac-associated proteins and genes, cardiac ion channel genes, as well as increased SERCA activity and a Raman fingerprint with the presence of maturation-associated peaks similar to primary CMs. We present a bioreactor platform that can serve as a foundation for the development of human-based cardiac in vitro models to verify drug candidates, and facilitates the study of cardiovascular development and disease.