HLA-Ehigh/HLA-Ghigh/HLA-IIlow Human iPSC-Derived Cardiomyocytes Exhibit Low Immunogenicity for Heart Regeneration

Yi Hsien Fang, Saprina P.H. Wang, I. Chuang Liao, Kuen Jer Tsai, Po Hsien Huang, Pei Jung Yang, Chia Jui Yen, Ping Yen Liu, Yan Shen Shan, Yen Wen Liu

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Although human pluripotent stem cells (hPSCs)-derived cardiomyocytes (hPSC-CMs) can remuscularize infarcted hearts and restore post-infarct cardiac function, post-transplant rejection resulting from human leukocyte antigen (HLA) mismatching is an enormous obstacle. It is crucial to identify hypoimmunogenic hPSCs for allogeneic cell therapy. This study is conducted to demonstrate the immune privilege of HLA-Ehigh/HLA-Ghigh/HLA-IIlow human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs). Ischemia-reperfusion surgery is done to create transmural myocardial infarction in rats. At post-infarct 4 days, hPSC-CMs (1.0×107 cells per kg), including human embryonic stem cell-derived cardiomyocytes (hESC-CMs), HLA-Elow/HLA-Glow/HLA-IIhigh hiPSC-CMs, and HLA-Ehigh/HLA-Ghigh/HLA-IIlow hiPSC-CMs, are injected into the infarcted myocardium. Under the treatment of very low dose cyclosporine A (CsA), only HLA-Ehigh/HLA-Ghigh/HLA-IIlow hiPSC-CMs survive in vivo and improved post-infarct cardiac function with infarct size reduction. HLA-Ehigh/HLA-Ghigh/HLA-IIlow hiPSC-CMs activate the SHP-1 signaling pathway of natural killer (NK) cells and cytotoxic T cells to evade attack by NK cells and cytotoxic T cells. Herein, it is demonstrated that using a clinically relevant CsA dose, HLA-Ehigh/HLA-Ghigh/HLA-IIlow hiPSC-CMs repair the infarcted myocardium and restore the post-infarct heart function. HLA-Ehigh/HLA-Ghigh/HLA-IIlow hiPSCs are less immunogenic and may serve as platforms for regeneration medicine.

Original languageEnglish
Article number2301186
JournalAdvanced Healthcare Materials
Volume12
Issue number29
DOIs
Publication statusPublished - 2023 Nov 22

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

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