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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
Takizawa, Hitoshi
Eto, Koji
Sugimoto, Naoshi
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: 26-Dec-2019
Publisher: Elsevier BV
Journal title: Stem Cell Reports
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: http://www.kyoto-u.ac.jp/ja/research/research_results/2019/191227_3.html
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