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Title: iPSC-Derived Platelets Depleted of HLA Class I Are Inert to Anti-HLA Class I and Natural Killer Cell Immunity
Authors: Suzuki, Daisuke
Flahou, Charlotte
Yoshikawa, Norihide
Stirblyte, Ieva
Hayashi, Yoshikazu
Sawaguchi, Akira
Akasaka, Marina
Nakamura, Sou
Higashi, Natsumi
Xu, Huaigeng
Matsumoto, Takuya
Fujio, Kosuke
Manz, Markus G.
Hotta, Akitsu  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-2619-7441 (unconfirmed)
Takizawa, Hitoshi
Eto, Koji
Sugimoto, Naoshi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-7271-9175 (unconfirmed)
Author's alias: 鈴木, 大助
吉川, 典秀
林, 慶和
澤口, 朗
中村, 壮
東, 奈津美
松本, 拓也
藤尾, 康祐
堀田, 秋津
滝澤, 仁
江藤, 浩之
杉本, 直志
Keywords: platelet
megakaryocyte
iPSC
HLA class I
natural killer cell
regenerative medicine
imMKCL
platelet transfusion
refractoriness
MSTRG mice
IL-15
Issue Date: 14-Jan-2020
Publisher: Elsevier BV
Journal title: Stem Cell Reports
Volume: 14
Issue: 1
Start page: 49
End page: 59
Abstract: The ex vivo production of platelets depleted of human leukocyte antigen class I (HLA-I) could serve as a universal measure to overcome platelet transfusion refractoriness caused by HLA-I incompatibility. Here, we developed human induced pluripotent cell-derived HLA-I-deficient platelets (HLA-KO iPLATs) in a clinically applicable imMKCL system by genetic manipulation and assessed their immunogenic properties including natural killer (NK) cells, which reject HLA-I downregulated cells. HLA-KO iPLATs were deficient for all HLA-I but did not elicit a cytotoxic response by NK cells in vitro and showed circulation equal to wild-type iPLATs upon transfusion in our newly established Hu-NK-MSTRG mice reconstituted with human NK cells. Additionally, HLA-KO iPLATs successfully circulated in an alloimmune platelet transfusion refractoriness model of Hu-NK-MISTRG mice. Mechanistically, the lack of NK cell-activating ligands on platelets may be responsible for evading the NK cell response. This study revealed the unique non-immunogenic property of platelets and provides a proof of concept for the clinical application of HLA-KO iPLATs.
Description: ゲノム編集技術を用いてiPS細胞から「ユニバーサル」な血小板の作製に成功. 京都大学プレスリリース. 2020-01-07.
Rights: © 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
URI: http://hdl.handle.net/2433/245275
DOI(Published Version): 10.1016/j.stemcr.2019.11.011
PubMed ID: 31883921
Related Link: https://www.kyoto-u.ac.jp/ja/research-news/2020-01-07
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