|Title:||iPSC-Derived Platelets Depleted of HLA Class I Are Inert to Anti-HLA Class I and Natural Killer Cell Immunity|
Manz, Markus G.
Hotta, Akitsu https://orcid.org/0000-0002-2619-7441 (unconfirmed)
Sugimoto, Naoshi https://orcid.org/0000-0002-7271-9175 (unconfirmed)
|Author's alias:||鈴木, 大助|
HLA class I
natural killer cell
|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/).|
|Appears in Collections:||Journal Articles|
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