| Autor: |
Fang, Yi‐Hsien, Wang, Saprina P. H., Liao, I‐Chuang, Tsai, Kuen‐Jer, Huang, Po‐Hsien, Yang, Pei‐Jung, Yen, Chia‐Jui, Liu, Ping‐Yen, Shan, Yan‐Shen, Liu, Yen‐Wen |
| Zdroj: |
Advanced Healthcare Materials; November 2023, Vol. 12 Issue: 29 |
| Abstrakt: |
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‐IIlowhuman 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 (1.0×107cells 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‐IIlowhiPSC‐CMs, are injected into the infarcted myocardium. Under the treatment of very low dose cyclosporine A (CsA), only HLA‐Ehigh/HLA‐Ghigh/HLA‐IIlowhiPSC‐CMs survive in vivo and improved post‐infarct cardiac function with infarct size reduction. HLA‐Ehigh/HLA‐Ghigh/HLA‐IIlowhiPSC‐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‐IIlowhiPSC‐CMs repair the infarcted myocardium and restore the post‐infarct heart function. HLA‐Ehigh/HLA‐Ghigh/HLA‐IIlowhiPSCs are less immunogenic and may serve as platforms for regeneration medicine. Under treatment with a clinically relevant immunosuppressant dose, xenotransplanted HLA‐Ehigh/HLA‐Ghigh/HLA‐IIlowhuman iPSC‐derived cardiomyocytes (hiPSC‐CMs) can effectively improve the post‐infarct cardiac function and repair damaged heart tissue because engrafted hiPSC‐CMs evade natural killer (NK) cells and cytotoxic T (Tc) cells by activating the SHP‐1/SHP‐2 signaling pathway of NK cells and Tc cells. |
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