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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: | 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 |
Appears in Collections: | Journal Articles |

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