PMID- 33897711
OWN - NLM
STAT- MEDLINE
DCOM- 20211014
LR  - 20211014
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Fit-For-All iPSC-Derived Cell Therapies and Their Evaluation in Humanized Mice 
      With NK Cell Immunity.
PG  - 662360
LID - 10.3389/fimmu.2021.662360 [doi]
LID - 662360
AB  - Human induced pluripotent stem cells (iPSCs) can be limitlessly expanded and 
      differentiated into almost all cell types. Moreover, they are amenable to gene 
      manipulation and, because they are established from somatic cells, can be 
      established from essentially any person. Based on these characteristics, iPSCs 
      have been extensively studied as cell sources for tissue grafts, blood 
      transfusions and cancer immunotherapies, and related clinical trials have 
      started. From an immune-matching perspective, autologous iPSCs are perfectly 
      compatible in principle, but also require a prolonged time for reaching the final 
      products, have high cost, and person-to-person variation hindering their common 
      use. Therefore, certified iPSCs with reduced immunogenicity are expected to 
      become off-the-shelf sources, such as those made from human leukocyte antigen 
      (HLA)-homozygous individuals or genetically modified for HLA depletion. 
      Preclinical tests using immunodeficient mice reconstituted with a human immune 
      system (HIS) serve as an important tool to assess the human alloresponse against 
      iPSC-derived cells. Especially, HIS mice reconstituted with not only human T 
      cells but also human natural killer (NK) cells are considered crucial. NK cells 
      attack so-called "missing self" cells that do not express self HLA class I, which 
      include HLA-homozygous cells that express only one allele type and HLA-depleted 
      cells. However, conventional HIS mice lack enough reconstituted human NK cells 
      for these tests. Several measures have been developed to overcome this issue 
      including the administration of cytokines that enhance NK cell expansion, such as 
      IL-2 and IL-15, the administration of vectors that express those cytokines, and 
      genetic manipulation to express the cytokines or to enhance the reconstitution of 
      human myeloid cells that express IL15R-alpha. Using such HIS mice with enhanced 
      human NK cell reconstitution, alloresponses against HLA-homozygous and 
      HLA-depleted cells have been studied. However, most studies used 
      HLA-downregulated tumor cells as the target cells and tested in vitro after 
      purifying human cells from HIS mice. In this review, we give an overview of the 
      current state of iPSCs in cell therapies, strategies to lessen their immunogenic 
      potential, and then expound on the development of HIS mice with reconstituted NK 
      cells, followed by their utilization in evaluating future universal 
      HLA-engineered iPSC-derived cells.
CI  - Copyright (c) 2021 Flahou, Morishima, Takizawa and Sugimoto.
FAU - Flahou, Charlotte
AU  - Flahou C
AD  - Department of Clinical Application, Center for iPS Cell Research and Application 
      (CiRA), Kyoto University, Kyoto, Japan.
FAU - Morishima, Tatsuya
AU  - Morishima T
AD  - Laboratory of Stem Cell Stress, International Research Center for Medical 
      Sciences (IRCMS), Kumamoto University, Kumamoto, Japan.
AD  - Laboratory of Hematopoietic Stem Cell Engineering, International Research Center 
      for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan.
FAU - Takizawa, Hitoshi
AU  - Takizawa H
AD  - Laboratory of Stem Cell Stress, International Research Center for Medical 
      Sciences (IRCMS), Kumamoto University, Kumamoto, Japan.
FAU - Sugimoto, Naoshi
AU  - Sugimoto N
AD  - Department of Clinical Application, Center for iPS Cell Research and Application 
      (CiRA), Kyoto University, Kyoto, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210402
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell- and Tissue-Based Therapy/*methods/standards
MH  - Cytotoxicity, Immunologic
MH  - HLA Antigens/immunology
MH  - Humans
MH  - Induced Pluripotent Stem Cells/*immunology
MH  - Killer Cells, Natural/*immunology
MH  - Mice
MH  - Mice, Transgenic
MH  - T-Lymphocytes/immunology
PMC - PMC8059435
OTO - NOTNLM
OT  - human induced pluripotent stem cells
OT  - human leukocyte antigen
OT  - humanized mice
OT  - natural killer cells
OT  - regenerative medicine
COIS- NS has applied for patents related to this manuscript. The remaining 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- 2021/04/27 06:00
MHDA- 2021/10/15 06:00
PMCR- 2021/01/01
CRDT- 2021/04/26 05:49
PHST- 2021/02/01 00:00 [received]
PHST- 2021/03/17 00:00 [accepted]
PHST- 2021/04/26 05:49 [entrez]
PHST- 2021/04/27 06:00 [pubmed]
PHST- 2021/10/15 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.662360 [doi]
PST - epublish
SO  - Front Immunol. 2021 Apr 2;12:662360. doi: 10.3389/fimmu.2021.662360. eCollection 
      2021.