PMID- 36032723
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220830
IS  - 2296-4185 (Print)
IS  - 2296-4185 (Electronic)
IS  - 2296-4185 (Linking)
VI  - 10
DP  - 2022
TI  - Maintenance of Hypoimmunogenic Features via Regulation of Endogenous Antigen 
      Processing and Presentation Machinery.
PG  - 936584
LID - 10.3389/fbioe.2022.936584 [doi]
LID - 936584
AB  - Universally acceptable donor cells have been developed to address the unmet need 
      for immunotypically matched materials for regenerative medicine. Since forced 
      expression of hypoimmunogenic genes represses the immune response, we established 
      universal pluripotent stem cells (PSCs) by replacing endogenous beta2-microglobulin 
      (beta2m) with beta2m directly conjugated to human leukocyte antigen (HLA)-G, thereby 
      simultaneously suppressing HLA-I expression and the natural killer (NK) 
      cell-mediated immune response. These modified human PSCs retained their 
      pluripotency and differentiation capacity; however, surface presentation of HLA-G 
      was absent from subsequently differentiated cells, particularly cells of neural 
      lineages, due to the downregulation of antigen processing and presentation 
      machinery (APM) genes. Induction of APM genes by overexpression of NLR-family 
      CARD domain-containing 5 (NLRC5) or activator subunit of nuclear factor kappa B 
      (NF-kappaB) heterodimer (RelA) recovered the surface expression of HLA-G and the 
      hypoimmunogenicity of neural cells. Our findings enhance the utility of 
      hypoimmunogenic cells as universal donors and will contribute to the development 
      of off-the-shelf stem-cell therapeutics.
CI  - Copyright (c) 2022 An, Koh, Ahn, Kim, Han, Lee, Kim and Lee.
FAU - An, Ju-Hyun
AU  - An JH
AD  - Futuristic Animal Resource and Research Center (FARRC), Korea Research Institute 
      of Bioscience and Biotechnology (KRIBB), Ochang, South Korea.
AD  - Department of Functional Genomics, KRIBB School of Bioscience, Korea University 
      of Science and Technology, Daejeon, South Korea.
FAU - Koh, Hyebin
AU  - Koh H
AD  - Futuristic Animal Resource and Research Center (FARRC), Korea Research Institute 
      of Bioscience and Biotechnology (KRIBB), Ochang, South Korea.
AD  - Department of Functional Genomics, KRIBB School of Bioscience, Korea University 
      of Science and Technology, Daejeon, South Korea.
FAU - Ahn, Yujin
AU  - Ahn Y
AD  - Futuristic Animal Resource and Research Center (FARRC), Korea Research Institute 
      of Bioscience and Biotechnology (KRIBB), Ochang, South Korea.
AD  - Department of Functional Genomics, KRIBB School of Bioscience, Korea University 
      of Science and Technology, Daejeon, South Korea.
FAU - Kim, Jieun
AU  - Kim J
AD  - Department of Medical Life Sciences, College of Medicine, The Catholic University 
      of Korea, Seoul, South Korea.
AD  - National Primate Research Center (NPRC), Korea Research Institute of Bioscience 
      and Biotechnology (KRIBB), Ochang, South Korea.
FAU - Han, A-Reum
AU  - Han AR
AD  - CHA Advanced Research Institute, Bundang CHA Hospital, CHA University, Seongnam, 
      South Korea.
FAU - Lee, Ji Yoon
AU  - Lee JY
AD  - CHA Advanced Research Institute, Bundang CHA Hospital, CHA University, Seongnam, 
      South Korea.
FAU - Kim, Sun-Uk
AU  - Kim SU
AD  - Futuristic Animal Resource and Research Center (FARRC), Korea Research Institute 
      of Bioscience and Biotechnology (KRIBB), Ochang, South Korea.
AD  - Department of Functional Genomics, KRIBB School of Bioscience, Korea University 
      of Science and Technology, Daejeon, South Korea.
FAU - Lee, Jong-Hee
AU  - Lee JH
AD  - Department of Functional Genomics, KRIBB School of Bioscience, Korea University 
      of Science and Technology, Daejeon, South Korea.
AD  - National Primate Research Center (NPRC), Korea Research Institute of Bioscience 
      and Biotechnology (KRIBB), Ochang, South Korea.
LA  - eng
PT  - Journal Article
DEP - 20220722
PL  - Switzerland
TA  - Front Bioeng Biotechnol
JT  - Frontiers in bioengineering and biotechnology
JID - 101632513
PMC - PMC9416868
OTO - NOTNLM
OT  - antigen presentation and processing machinery
OT  - cell therapy
OT  - hypoimmunogenic cell
OT  - regenerative cell therapy
OT  - universal donor cell
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/08/30 06:00
MHDA- 2022/08/30 06:01
PMCR- 2022/01/01
CRDT- 2022/08/29 04:45
PHST- 2022/05/05 00:00 [received]
PHST- 2022/06/16 00:00 [accepted]
PHST- 2022/08/29 04:45 [entrez]
PHST- 2022/08/30 06:00 [pubmed]
PHST- 2022/08/30 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 936584 [pii]
AID - 10.3389/fbioe.2022.936584 [doi]
PST - epublish
SO  - Front Bioeng Biotechnol. 2022 Jul 22;10:936584. doi: 10.3389/fbioe.2022.936584. 
      eCollection 2022.