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Maturation of induced pluripotent stem cell-derived cardiomyocytes and its therapeutic effect on myocardial infarction in mouse.

Authors
  • Wu, Peng1, 2
  • Sai, Xiyalatu1, 2
  • Li, Zhetao1, 2
  • Ye, Xing1, 2
  • Jin, Li3
  • Liu, Guihuan4
  • Li, Ge2, 5
  • Yang, Pingzhen3
  • Zhao, Mingyi2, 5
  • Zhu, Shuoji2, 5
  • Liu, Nanbo2, 5
  • Zhu, Ping1, 2, 5
  • 1 The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China. , (China)
  • 2 Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510100, China. , (China)
  • 3 Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China. , (China)
  • 4 Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, 510080, China. , (China)
  • 5 Guangdong Provincial Key Laboratory of Pathogenesis, Targeted Prevention and Treatment of Heart Disease, Guangzhou, 510100, China. , (China)
Type
Published Article
Journal
Bioactive Materials
Publisher
KeAi Publishing
Publication Date
Feb 01, 2023
Volume
20
Pages
286–305
Identifiers
DOI: 10.1016/j.bioactmat.2022.05.024
PMID: 35702609
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have an irreplaceable role in the treatment of myocardial infarction (MI), which can be injected into the transplanted area with new cardiomyocytes (Cardiomyocytes, CMs), and improve myocardial function. However, the immaturity of the structure and function of iPSC-CMs is the main bottleneck at present. Since collagen participates in the formation of extracellular matrix (ECM), we synthesized nano colloidal gelatin (Gel) with collagen as the main component, and confirmed that the biomaterial has good biocompatibility and is suitable for cellular in vitro growth. Subsequently, we combined the PI3K/AKT/mTOR pathway inhibitor BEZ-235 with Gel and found that the two combined increased the sarcomere length and action potential amplitude (APA) of iPSC-CMs, and improved the Ca2+ processing ability, the maturation of mitochondrial morphological structure and metabolic function. Not only that, Gel can also prolong the retention rate of iPSC-CMs in the myocardium and increase the expression of Cx43 and angiogenesis in the transplanted area of mature iPSC-CMs, which also provides a reliable basis for the subsequent treatment of mature iPSC-CMs. © 2022 The Authors.

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