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

Stem Cell Reports
Nian ShenKatja Schenke-Layland

Abstract

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.

Citations

Mar 21, 2018·Journal of Cardiovascular Translational Research·Shi Hua Tan, Lei Ye
May 30, 2019·Bioengineering·Minh Nguyen Tuyet Le, Kouichi Hasegawa
Apr 30, 2019·Tissue Engineering. Part a·Peter Loskill, Nathaniel Huebsch
Oct 25, 2020·Stem Cell Reviews and Reports·Pallavi PushpMukesh Kumar Gupta
Nov 25, 2020·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Rui ZhangFeng Lan
Mar 2, 2021·Advanced Science·Aline ZbindenKatja Schenke-Layland
Jun 20, 2021·Seminars in Cell & Developmental Biology·Megan RowtonIvan P Moskowitz
Aug 17, 2021·Journal of Biomedical Materials Research. Part a·Xinyue ChuXiong Xiao
Mar 23, 2021··Ghulsan Fahmi El BayaniMuhammad Hanif Nadhif

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Methods Mentioned

BETA
flow cytometry
PCA

Software Mentioned

COMSOL
COMSOL Multiphysics
SolidWorks
ImageJ

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