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

Author:

Fang Yi‐Hsien12,Wang Saprina P. H.23,Liao I‐Chuang4,Tsai Kuen‐Jer12,Huang Po‐Hsien25,Yang Pei‐Jung23,Yen Chia‐Jui26,Liu Ping‐Yen13,Shan Yan‐Shen127,Liu Yen‐Wen123ORCID

Affiliation:

1. Institute of Clinical Medicine College of Medicine National Cheng Kung University Tainan 70401 Taiwan

2. Center of Cell Therapy National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 70403 Taiwan

3. Division of Cardiology Department of Internal Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 70403 Taiwan

4. Department of Pathology Chi‐Mei Medical Center Tainan 71004 Taiwan

5. Institute of Basic Medical Sciences College of Medicine National Cheng Kung University Tainan 70101 Taiwan

6. Department of Oncology National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 70403 Taiwan

7. Department of Surgery National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan 70403 Taiwan

Abstract

AbstractAlthough 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.

Funder

Ministry of Science and Technology, Taiwan

National Science and Technology Council

National Cheng Kung University Hospital

Publisher

Wiley

Subject

Pharmaceutical Science,Biomedical Engineering,Biomaterials

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3