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Steps toward Maturation of Embryonic Stem Cell-Derived Cardiomyocytes by Defined Physical Signals

Shen, N., Knopf, A., Westendorf, C., Kraushaar, U., Riedl, J., Bauer, H., Poschel, S., Layland, S. L., Holeiter, M., Knolle, S., Brauchle, E., Nsair, A., Hinderer, S., Schenke-Layland, K. (2017).

Stem Cell Reports. 2017 May 18. pii: S2213-6711(17)30175-3. doi: 10.1016/j.stemcr.2017.04.021.

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.

Pubmed

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