PMID- 37672681
OWN - NLM
STAT- MEDLINE
DCOM- 20231123
LR  - 20231213
IS  - 2192-2659 (Electronic)
IS  - 2192-2640 (Linking)
VI  - 12
IP  - 29
DP  - 2023 Nov
TI  - HLA-E(high) /HLA-G(high) /HLA-II(low) Human iPSC-Derived Cardiomyocytes Exhibit 
      Low Immunogenicity for Heart Regeneration.
PG  - e2301186
LID - 10.1002/adhm.202301186 [doi]
AB  - 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-E(high) /HLA-G(high) /HLA-II(low) 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 (1.0x10(7) cells per kg), including 
      human embryonic stem cell-derived cardiomyocytes (hESC-CMs), 
      HLA-Elow/HLA-Glow/HLA-IIhigh hiPSC-CMs, and HLA-E(high) /HLA-G(high) /HLA-II(low) 
      hiPSC-CMs, are injected into the infarcted myocardium. Under the treatment of 
      very low dose cyclosporine A (CsA), only HLA-E(high) /HLA-G(high) /HLA-II(low) 
      hiPSC-CMs survive in vivo and improved post-infarct cardiac function with infarct 
      size reduction. HLA-E(high) /HLA-G(high) /HLA-II(low) 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-E(high) /HLA-G(high) /HLA-II(low) 
      hiPSC-CMs repair the infarcted myocardium and restore the post-infarct heart 
      function. HLA-E(high) /HLA-G(high) /HLA-II(low) hiPSCs are less immunogenic and 
      may serve as platforms for regeneration medicine.
CI  - (c) 2023 Wiley-VCH GmbH.
FAU - Fang, Yi-Hsien
AU  - Fang YH
AD  - Institute of Clinical Medicine, College of Medicine, National Cheng Kung 
      University, Tainan, 70401, Taiwan.
AD  - Center of Cell Therapy, National Cheng Kung University Hospital, College of 
      Medicine, National Cheng Kung University, Tainan, 70403, Taiwan.
FAU - Wang, Saprina P H
AU  - Wang SPH
AD  - Center of Cell Therapy, National Cheng Kung University Hospital, College of 
      Medicine, National Cheng Kung University, Tainan, 70403, Taiwan.
AD  - Division of Cardiology, Department of Internal Medicine, National Cheng Kung 
      University Hospital, College of Medicine, National Cheng Kung University, Tainan, 
      70403, Taiwan.
FAU - Liao, I-Chuang
AU  - Liao IC
AD  - Department of Pathology, Chi-Mei Medical Center, Tainan, 71004, Taiwan.
FAU - Tsai, Kuen-Jer
AU  - Tsai KJ
AD  - Institute of Clinical Medicine, College of Medicine, National Cheng Kung 
      University, Tainan, 70401, Taiwan.
AD  - Center of Cell Therapy, National Cheng Kung University Hospital, College of 
      Medicine, National Cheng Kung University, Tainan, 70403, Taiwan.
FAU - Huang, Po-Hsien
AU  - Huang PH
AD  - Center of Cell Therapy, National Cheng Kung University Hospital, College of 
      Medicine, National Cheng Kung University, Tainan, 70403, Taiwan.
AD  - Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung 
      University, Tainan, 70101, Taiwan.
FAU - Yang, Pei-Jung
AU  - Yang PJ
AD  - Center of Cell Therapy, National Cheng Kung University Hospital, College of 
      Medicine, National Cheng Kung University, Tainan, 70403, Taiwan.
AD  - Division of Cardiology, Department of Internal Medicine, National Cheng Kung 
      University Hospital, College of Medicine, National Cheng Kung University, Tainan, 
      70403, Taiwan.
FAU - Yen, Chia-Jui
AU  - Yen CJ
AD  - Center of Cell Therapy, National Cheng Kung University Hospital, College of 
      Medicine, National Cheng Kung University, Tainan, 70403, Taiwan.
AD  - Department of Oncology, National Cheng Kung University Hospital, College of 
      Medicine, National Cheng Kung University, Tainan, 70403, Taiwan.
FAU - Liu, Ping-Yen
AU  - Liu PY
AD  - Institute of Clinical Medicine, College of Medicine, National Cheng Kung 
      University, Tainan, 70401, Taiwan.
AD  - Division of Cardiology, Department of Internal Medicine, National Cheng Kung 
      University Hospital, College of Medicine, National Cheng Kung University, Tainan, 
      70403, Taiwan.
FAU - Shan, Yan-Shen
AU  - Shan YS
AD  - Institute of Clinical Medicine, College of Medicine, National Cheng Kung 
      University, Tainan, 70401, Taiwan.
AD  - Center of Cell Therapy, National Cheng Kung University Hospital, College of 
      Medicine, National Cheng Kung University, Tainan, 70403, Taiwan.
AD  - Department of Surgery, National Cheng Kung University Hospital, College of 
      Medicine, National Cheng Kung University, Tainan, 70403, Taiwan.
FAU - Liu, Yen-Wen
AU  - Liu YW
AUID- ORCID: 0000-0003-4662-628X
AD  - Institute of Clinical Medicine, College of Medicine, National Cheng Kung 
      University, Tainan, 70401, Taiwan.
AD  - Center of Cell Therapy, National Cheng Kung University Hospital, College of 
      Medicine, National Cheng Kung University, Tainan, 70403, Taiwan.
AD  - Division of Cardiology, Department of Internal Medicine, National Cheng Kung 
      University Hospital, College of Medicine, National Cheng Kung University, Tainan, 
      70403, Taiwan.
LA  - eng
GR  - MOST 109-2628-B-006-028/Ministry of Science and Technology, Taiwan/
GR  - 110-2628-B-006-026/Ministry of Science and Technology, Taiwan/
GR  - 111-2321-B006-013/Ministry of Science and Technology, Taiwan/
GR  - NSTC 112-2321-B-006-012/National Science and Technology Council, Taiwan/
GR  - NCKUH-10809017/National Cheng Kung University Hospital/
GR  - 10909027/National Cheng Kung University Hospital/
GR  - 110009024/National Cheng Kung University Hospital/
GR  - 11109014/National Cheng Kung University Hospital/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230920
PL  - Germany
TA  - Adv Healthc Mater
JT  - Advanced healthcare materials
JID - 101581613
RN  - 0 (HLA-G Antigens)
SB  - IM
MH  - Humans
MH  - Rats
MH  - Animals
MH  - Myocytes, Cardiac/metabolism
MH  - *Induced Pluripotent Stem Cells/metabolism
MH  - HLA-G Antigens/metabolism
MH  - *Myocardial Infarction/therapy
MH  - Regeneration
MH  - Cell Differentiation
MH  - HLA-E Antigens
OTO - NOTNLM
OT  - amniotic fluid stem cells
OT  - cardiac regeneration
OT  - cardiomyocytes
OT  - human leukocyte antigens
OT  - immunogenicity
OT  - pluripotent stem cells
EDAT- 2023/09/06 18:41
MHDA- 2023/11/23 06:42
CRDT- 2023/09/06 15:13
PHST- 2023/08/31 00:00 [revised]
PHST- 2023/04/14 00:00 [received]
PHST- 2023/11/23 06:42 [medline]
PHST- 2023/09/06 18:41 [pubmed]
PHST- 2023/09/06 15:13 [entrez]
AID - 10.1002/adhm.202301186 [doi]
PST - ppublish
SO  - Adv Healthc Mater. 2023 Nov;12(29):e2301186. doi: 10.1002/adhm.202301186. Epub 
      2023 Sep 20.