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Comparison of Non-human Primate versus Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Treatment of Myocardial Infarction.

  • Author(s): Zhao, Xin
  • Chen, Haodong
  • Xiao, Dan
  • Yang, Huaxiao
  • Itzhaki, Ilanit
  • Qin, Xulei
  • Chour, Tony
  • Aguirre, Aitor
  • Lehmann, Kim
  • Kim, Youngkyun
  • Shukla, Praveen
  • Holmström, Alexandra
  • Zhang, Joe Z
  • Zhuge, Yan
  • Ndoye, Babacar C
  • Zhao, Mingtao
  • Neofytou, Evgenios
  • Zimmermann, Wolfram-Hubertus
  • Jain, Mohit
  • Wu, Joseph C
  • et al.
Abstract

Non-human primates (NHPs) can serve as a human-like model to study cell therapy using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). However, whether the efficacy of NHP and human iPSC-CMs is mechanistically similar remains unknown. To examine this, RNU rats received intramyocardial injection of 1 × 107 NHP or human iPSC-CMs or the same number of respective fibroblasts or PBS control (n = 9-14/group) at 4 days after 60-min coronary artery occlusion-reperfusion. Cardiac function and left ventricular remodeling were similarly improved in both iPSC-CM-treated groups. To mimic the ischemic environment in the infarcted heart, both cultured NHP and human iPSC-CMs underwent 24-hr hypoxia in vitro. Both cells and media were collected, and similarities in transcriptomic as well as metabolomic profiles were noted between both groups. In conclusion, both NHP and human iPSC-CMs confer similar cardioprotection in a rodent myocardial infarction model through relatively similar mechanisms via promotion of cell survival, angiogenesis, and inhibition of hypertrophy and fibrosis.

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