Transferrin improved the generation of cardiomyocyte from human pluripotent stem cells for myocardial infarction repair
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ORIGINAL PAPER
Transferrin improved the generation of cardiomyocyte from human pluripotent stem cells for myocardial infarction repair Fengzhi Zhang1 · Hui Qiu2 · Xiaohui Dong1 · Chunlan Wang1 · Jie Na2 · Jin Zhou1 · Changyong Wang1 Received: 20 July 2020 / Accepted: 3 November 2020 © The Author(s) 2020
Abstract Human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) hold great promise for the repair of the injured heart, but optimal cell production in a fully chemically defined and cost-effective system is essential for the efficacy and safety of cell transplantation therapies. In this study, we provided a simple and efficient strategy for cardiac differentiation from hPSCs and performed functional evaluation in a rat model of myocardial infarction. Using a chemically defined medium including four components, recombinant human albumin, ascorbic acid, human transferrin, and RPMI 1640, we developed a manageable and cost-effective protocol for robust generation of CMs from hPSCs. Interestingly, the addition of transferrin helped hPSCs to transit from TeSR-E8 medium to the simple cardiac differentiation medium and successfully initiated mesoderm differentiation without significant cell death. The CM generation efficiency was up to 85% based on cTnT expression. We performed transcriptome profiling from differentiation day 0 to 35, and characterized interesting dynamic change of cardiac genes. CMs derived from transferrin-supplemented simple medium have similar transcriptome and the maturation level compared to those generated in B27 minus insulin medium as well as their in vivo counterparts. Importantly, after transplantation, hPSC-derived CMs survived in the infarcted rat heart, significantly improved the physiological function and reduced fibrosis. Our study offers an easy-to-use and cost-effective method for cardiac differentiation and facilitates the translational application of hPSC-derived CMs for heart repair. Keywords hPSC · Cardiomyocyte · Chemically defined · Transferrin · Myocardial infarction
Introduction Adult mammalian hearts have a limited regenerative capacity, consequently, loss of cardiomyocytes is a leading cause of heart failure (Laflamme and Murry 2011; Weinberger and Eschenhagen 2020). Cardiomyocyte transplantation is a straight forward approach for cardiac repair and human pluripotent stem cells (hPSCs) offer an attractive cell source for cardiomyocyte generation. hPSCs, including human Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10735-020-09926-0) contains supplementary material, which is available to authorized users. * Changyong Wang [email protected] 1
Department of Neural Engineering and Biological Interdisciplinary Studies, Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, China
School of Medicine, Tsinghua University, Beijing, China
2
embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) (Thomson et al. 1998;
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