PMID- 32197113
OWN - NLM
STAT- MEDLINE
DCOM- 20210205
LR  - 20210205
IS  - 2213-6711 (Electronic)
IS  - 2213-6711 (Linking)
VI  - 14
IP  - 4
DP  - 2020 Apr 14
TI  - Generation of Retinal Pigment Epithelial Cells Derived from Human Embryonic Stem 
      Cells Lacking Human Leukocyte Antigen Class I and II.
PG  - 648-662
LID - S2213-6711(20)30062-X [pii]
LID - 10.1016/j.stemcr.2020.02.006 [doi]
AB  - Human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells 
      could serve as a replacement therapy in advanced stages of age-related macular 
      degeneration. However, allogenic hESC-RPE transplants trigger immune rejection, 
      supporting a strategy to evade their immune recognition. We established 
      single-knockout beta-2 microglobulin (SKO-B2M), class II major histocompatibility 
      complex transactivator (SKO-CIITA) and double-knockout (DKO) hESC lines that were 
      further differentiated into corresponding hESC-RPE lines lacking either surface 
      human leukocyte antigen class I (HLA-I) or HLA-II, or both. Activation of CD4+ 
      and CD8+ T-cells was markedly lower by hESC-RPE DKO cells, while natural killer 
      cell cytotoxic response was not increased. After transplantation of SKO-B2M, 
      SKO-CIITA, or DKO hESC-RPEs in a preclinical rabbit model, donor cell rejection 
      was reduced and delayed. In conclusion, we have developed cell lines that lack 
      both HLA-I and -II antigens, which evoke reduced T-cell responses in vitro 
      together with reduced rejection in a large-eyed animal model.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Petrus-Reurer, Sandra
AU  - Petrus-Reurer S
AD  - Clinical Neuroscience, Section for Ophtalmology and Vision, Karolinska 
      Institutet, St. Erik Eye Hospital, 11282 Stockholm, Sweden; Department of 
      Clinical Sciences, Intervention and Technology, Karolinska Insitutet, 17177 
      Stockholm, Sweden; Gynecology and Reproductive Medicine, Karolinska 
      Universitetssjukhuset, 14186 Stockholm, Sweden.
FAU - Winblad, Nerges
AU  - Winblad N
AD  - Department of Clinical Sciences, Intervention and Technology, Karolinska 
      Insitutet, 17177 Stockholm, Sweden; Gynecology and Reproductive Medicine, 
      Karolinska Universitetssjukhuset, 14186 Stockholm, Sweden.
FAU - Kumar, Pankaj
AU  - Kumar P
AD  - Department of Clinical Sciences, Intervention and Technology, Karolinska 
      Insitutet, 17177 Stockholm, Sweden; Gynecology and Reproductive Medicine, 
      Karolinska Universitetssjukhuset, 14186 Stockholm, Sweden.
FAU - Gorchs, Laia
AU  - Gorchs L
AD  - Department of Laboratory Medicine, Karolinska Institutet, 14152 Stockholm, 
      Sweden.
FAU - Chrobok, Michael
AU  - Chrobok M
AD  - Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, 
      Karolinska Institutet, 17177 Stockholm, Sweden.
FAU - Wagner, Arnika Kathleen
AU  - Wagner AK
AD  - Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, 
      Karolinska Institutet, 17177 Stockholm, Sweden.
FAU - Bartuma, Hammurabi
AU  - Bartuma H
AD  - Clinical Neuroscience, Section for Ophtalmology and Vision, Karolinska 
      Institutet, St. Erik Eye Hospital, 11282 Stockholm, Sweden.
FAU - Lardner, Emma
AU  - Lardner E
AD  - Clinical Neuroscience, Section for Ophtalmology and Vision, Karolinska 
      Institutet, St. Erik Eye Hospital, 11282 Stockholm, Sweden.
FAU - Aronsson, Monica
AU  - Aronsson M
AD  - Clinical Neuroscience, Section for Ophtalmology and Vision, Karolinska 
      Institutet, St. Erik Eye Hospital, 11282 Stockholm, Sweden.
FAU - Plaza Reyes, Alvaro
AU  - Plaza Reyes A
AD  - Department of Clinical Sciences, Intervention and Technology, Karolinska 
      Insitutet, 17177 Stockholm, Sweden; Gynecology and Reproductive Medicine, 
      Karolinska Universitetssjukhuset, 14186 Stockholm, Sweden.
FAU - Andre, Helder
AU  - Andre H
AD  - Clinical Neuroscience, Section for Ophtalmology and Vision, Karolinska 
      Institutet, St. Erik Eye Hospital, 11282 Stockholm, Sweden.
FAU - Alici, Evren
AU  - Alici E
AD  - Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, 
      Karolinska Institutet, 17177 Stockholm, Sweden.
FAU - Kaipe, Helen
AU  - Kaipe H
AD  - Department of Laboratory Medicine, Karolinska Institutet, 14152 Stockholm, 
      Sweden; Clinical Immunology and Transfusion Medicine, Karolinska University 
      Hospital, Huddinge, 14186 Stockholm, Sweden.
FAU - Kvanta, Anders
AU  - Kvanta A
AD  - Clinical Neuroscience, Section for Ophtalmology and Vision, Karolinska 
      Institutet, St. Erik Eye Hospital, 11282 Stockholm, Sweden.
FAU - Lanner, Fredrik
AU  - Lanner F
AD  - Department of Clinical Sciences, Intervention and Technology, Karolinska 
      Insitutet, 17177 Stockholm, Sweden; Gynecology and Reproductive Medicine, 
      Karolinska Universitetssjukhuset, 14186 Stockholm, Sweden; Ming Wai Lau Center 
      for Reparative Medicine, Stockholm Node, Karolinska Institutet, 17177 Stockholm, 
      Sweden. Electronic address: fredrik.lanner@ki.se.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200319
PL  - United States
TA  - Stem Cell Reports
JT  - Stem cell reports
JID - 101611300
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (MHC class II transactivator protein)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (beta 2-Microglobulin)
RN  - EC 3.1.- (CRISPR-Associated Protein 9)
SB  - IM
MH  - CRISPR-Associated Protein 9/metabolism
MH  - CRISPR-Cas Systems/genetics
MH  - Cytotoxicity, Immunologic
MH  - Epithelial Cells/*metabolism
MH  - Heterografts
MH  - Histocompatibility Antigens Class I/*metabolism
MH  - Histocompatibility Antigens Class II/*metabolism
MH  - Human Embryonic Stem Cells/*cytology/metabolism
MH  - Humans
MH  - Immunomodulation
MH  - Nuclear Proteins/metabolism
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Retinal Pigment Epithelium/*cytology
MH  - T-Lymphocytes/metabolism
MH  - Trans-Activators/metabolism
MH  - beta 2-Microglobulin/metabolism
PMC - PMC7160308
OTO - NOTNLM
OT  - HLA-I knockout
OT  - HLA-II knockout
OT  - cellular therapy
OT  - human embryonic stem cells
OT  - immune evasion
OT  - retinal pigment epithelium
OT  - subretinal injection
OT  - transplantation rejection
OT  - xenogeneic transplant
OT  - xenograft model
EDAT- 2020/03/21 06:00
MHDA- 2021/02/07 06:00
PMCR- 2020/03/19
CRDT- 2020/03/21 06:00
PHST- 2019/05/28 00:00 [received]
PHST- 2020/02/18 00:00 [revised]
PHST- 2020/02/19 00:00 [accepted]
PHST- 2020/03/21 06:00 [pubmed]
PHST- 2021/02/07 06:00 [medline]
PHST- 2020/03/21 06:00 [entrez]
PHST- 2020/03/19 00:00 [pmc-release]
AID - S2213-6711(20)30062-X [pii]
AID - 10.1016/j.stemcr.2020.02.006 [doi]
PST - ppublish
SO  - Stem Cell Reports. 2020 Apr 14;14(4):648-662. doi: 10.1016/j.stemcr.2020.02.006. 
      Epub 2020 Mar 19.