PMID- 33172291
OWN - NLM
STAT- MEDLINE
DCOM- 20210719
LR  - 20210719
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Print)
IS  - 0963-6897 (Linking)
VI  - 29
DP  - 2020 Jan-Dec
TI  - Generation of Mesenchymal Stromal Cells with Low Immunogenicity from Human 
      PBMC-Derived beta2 Microglobulin Knockout Induced Pluripotent Stem Cells.
PG  - 963689720965529
LID - 10.1177/0963689720965529 [doi]
LID - 0963689720965529
AB  - Mesenchymal stromal cells (MSCs) are viewed as immune-privileged cells and have 
      been broadly applied in allogeneic adoptive cell transfer for regenerative 
      medicine or immune-suppressing purpose. However, the surface expression of human 
      leukocyte antigen (HLA) class I molecules on MSCs could still possibly induce the 
      rejection of allogeneic MSCs from the recipients. Here, we disrupted the beta2 
      microglobulin (B2M) gene in human peripheral blood mononuclear cell-derived 
      induced pluripotent stem cells (iPSCs) with two clustered regulatory interspaced 
      short palindromic repeat (CRISPR)-associated Cas9 endonuclease-based methods. The 
      B2M knockout iPSCs did not express HLA class I molecules but maintained their 
      pluripotency and genome stability. Subsequently, MSCs were derived from the 
      HLA-negative iPSCs (iMSCs). We demonstrated that B2M knockout did not affect iMSC 
      phenotype, multipotency, and immune suppressive characteristics and, most 
      importantly, reduced iMSC immunogenicity to allogeneic peripheral blood 
      mononuclear cells. Thus, B2M knockout iPSCs could serve as unlimited 
      off-the-shelf cell resources in adoptive cell transfer, while the derived iMSCs 
      hold great potential as universal grafts in allogeneic MSC transplantation.
FAU - Zha, Shijun
AU  - Zha S
AUID- ORCID: 0000-0003-1903-9725
AD  - Department of Biological Sciences, National University of Singapore, Singapore.
FAU - Tay, Johan Chin-Kang
AU  - Tay JC
AD  - Department of Biological Sciences, National University of Singapore, Singapore.
FAU - Zhu, Sumin
AU  - Zhu S
AD  - Department of Biological Sciences, National University of Singapore, Singapore.
FAU - Li, Zhendong
AU  - Li Z
AD  - Department of Biological Sciences, National University of Singapore, Singapore.
FAU - Du, Zhicheng
AU  - Du Z
AD  - Department of Biological Sciences, National University of Singapore, Singapore.
FAU - Wang, Shu
AU  - Wang S
AD  - Department of Biological Sciences, National University of Singapore, Singapore.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
SB  - IM
MH  - Humans
MH  - Induced Pluripotent Stem Cells/*cytology/metabolism
MH  - Leukocytes, Mononuclear/cytology/metabolism
MH  - Mesenchymal Stem Cells/*cytology/metabolism
MH  - Regenerative Medicine/methods
MH  - Transplantation, Homologous
PMC - PMC7784598
OTO - NOTNLM
OT  - B2M
OT  - CRISPR/Cas9
OT  - HLA
OT  - iPSC-MSC
OT  - immunogenicity
COIS- Declaration of Conflicting Interests: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2020/11/12 06:00
MHDA- 2021/07/20 06:00
PMCR- 2020/11/10
CRDT- 2020/11/11 05:34
PHST- 2020/11/11 05:34 [entrez]
PHST- 2020/11/12 06:00 [pubmed]
PHST- 2021/07/20 06:00 [medline]
PHST- 2020/11/10 00:00 [pmc-release]
AID - 10.1177_0963689720965529 [pii]
AID - 10.1177/0963689720965529 [doi]
PST - ppublish
SO  - Cell Transplant. 2020 Jan-Dec;29:963689720965529. doi: 10.1177/0963689720965529.