iPSC-Derived Platelets Depleted of HLA Class I Are Inert to Anti-HLA Class I and Natural Killer Cell Immunity
Summary: 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 (HL...
Ausführliche Beschreibung
Autor*in: |
Daisuke Suzuki [verfasserIn] Charlotte Flahou [verfasserIn] Norihide Yoshikawa [verfasserIn] Ieva Stirblyte [verfasserIn] Yoshikazu Hayashi [verfasserIn] Akira Sawaguchi [verfasserIn] Marina Akasaka [verfasserIn] Sou Nakamura [verfasserIn] Natsumi Higashi [verfasserIn] Huaigeng Xu [verfasserIn] Takuya Matsumoto [verfasserIn] Kosuke Fujio [verfasserIn] Markus G. Manz [verfasserIn] Akitsu Hotta [verfasserIn] Hitoshi Takizawa [verfasserIn] Koji Eto [verfasserIn] Naoshi Sugimoto [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2020 |
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Übergeordnetes Werk: |
In: Stem Cell Reports - Elsevier, 2015, 14(2020), 1, Seite 49-59 |
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Übergeordnetes Werk: |
volume:14 ; year:2020 ; number:1 ; pages:49-59 |
Links: |
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DOI / URN: |
10.1016/j.stemcr.2019.11.011 |
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Katalog-ID: |
DOAJ006555985 |
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520 | |a Summary: 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. : T cells and antibodies or NK cells reject HLA-I-incompatible or HLA-I-deficient cells, respectively. Sugimoto and colleagues produced HLA-I null platelets from iPSCs in a clinically applicable system and found that platelets can circulate even in human NK cell-reconstituted mice. Potentially, universal HLA-KO platelets could treat patients suffering from platelet transfusion refractoriness caused by HLA-I incompatibility. Keywords: platelet, megakaryocyte, iPSC, HLA class I, natural killer cell, regenerative medicine, imMKCL, platelet transfusion, refractoriness, MSTRG mice, IL-15 | ||
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10.1016/j.stemcr.2019.11.011 doi (DE-627)DOAJ006555985 (DE-599)DOAJ9f437e1b02f6488582832358c907a1bf DE-627 ger DE-627 rakwb eng R5-920 QH301-705.5 Daisuke Suzuki verfasserin aut iPSC-Derived Platelets Depleted of HLA Class I Are Inert to Anti-HLA Class I and Natural Killer Cell Immunity 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: 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. : T cells and antibodies or NK cells reject HLA-I-incompatible or HLA-I-deficient cells, respectively. Sugimoto and colleagues produced HLA-I null platelets from iPSCs in a clinically applicable system and found that platelets can circulate even in human NK cell-reconstituted mice. Potentially, universal HLA-KO platelets could treat patients suffering from platelet transfusion refractoriness caused by HLA-I incompatibility. Keywords: platelet, megakaryocyte, iPSC, HLA class I, natural killer cell, regenerative medicine, imMKCL, platelet transfusion, refractoriness, MSTRG mice, IL-15 Medicine (General) Biology (General) Charlotte Flahou verfasserin aut Norihide Yoshikawa verfasserin aut Ieva Stirblyte verfasserin aut Yoshikazu Hayashi verfasserin aut Akira Sawaguchi verfasserin aut Marina Akasaka verfasserin aut Sou Nakamura verfasserin aut Natsumi Higashi verfasserin aut Huaigeng Xu verfasserin aut Takuya Matsumoto verfasserin aut Kosuke Fujio verfasserin aut Markus G. Manz verfasserin aut Akitsu Hotta verfasserin aut Hitoshi Takizawa verfasserin aut Koji Eto verfasserin aut Naoshi Sugimoto verfasserin aut In Stem Cell Reports Elsevier, 2015 14(2020), 1, Seite 49-59 (DE-627)749730862 (DE-600)2720528-9 22136711 nnns volume:14 year:2020 number:1 pages:49-59 https://doi.org/10.1016/j.stemcr.2019.11.011 kostenfrei https://doaj.org/article/9f437e1b02f6488582832358c907a1bf kostenfrei http://www.sciencedirect.com/science/article/pii/S221367111930414X kostenfrei https://doaj.org/toc/2213-6711 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 14 2020 1 49-59 |
spelling |
10.1016/j.stemcr.2019.11.011 doi (DE-627)DOAJ006555985 (DE-599)DOAJ9f437e1b02f6488582832358c907a1bf DE-627 ger DE-627 rakwb eng R5-920 QH301-705.5 Daisuke Suzuki verfasserin aut iPSC-Derived Platelets Depleted of HLA Class I Are Inert to Anti-HLA Class I and Natural Killer Cell Immunity 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: 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. : T cells and antibodies or NK cells reject HLA-I-incompatible or HLA-I-deficient cells, respectively. Sugimoto and colleagues produced HLA-I null platelets from iPSCs in a clinically applicable system and found that platelets can circulate even in human NK cell-reconstituted mice. Potentially, universal HLA-KO platelets could treat patients suffering from platelet transfusion refractoriness caused by HLA-I incompatibility. Keywords: platelet, megakaryocyte, iPSC, HLA class I, natural killer cell, regenerative medicine, imMKCL, platelet transfusion, refractoriness, MSTRG mice, IL-15 Medicine (General) Biology (General) Charlotte Flahou verfasserin aut Norihide Yoshikawa verfasserin aut Ieva Stirblyte verfasserin aut Yoshikazu Hayashi verfasserin aut Akira Sawaguchi verfasserin aut Marina Akasaka verfasserin aut Sou Nakamura verfasserin aut Natsumi Higashi verfasserin aut Huaigeng Xu verfasserin aut Takuya Matsumoto verfasserin aut Kosuke Fujio verfasserin aut Markus G. Manz verfasserin aut Akitsu Hotta verfasserin aut Hitoshi Takizawa verfasserin aut Koji Eto verfasserin aut Naoshi Sugimoto verfasserin aut In Stem Cell Reports Elsevier, 2015 14(2020), 1, Seite 49-59 (DE-627)749730862 (DE-600)2720528-9 22136711 nnns volume:14 year:2020 number:1 pages:49-59 https://doi.org/10.1016/j.stemcr.2019.11.011 kostenfrei https://doaj.org/article/9f437e1b02f6488582832358c907a1bf kostenfrei http://www.sciencedirect.com/science/article/pii/S221367111930414X kostenfrei https://doaj.org/toc/2213-6711 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 14 2020 1 49-59 |
allfields_unstemmed |
10.1016/j.stemcr.2019.11.011 doi (DE-627)DOAJ006555985 (DE-599)DOAJ9f437e1b02f6488582832358c907a1bf DE-627 ger DE-627 rakwb eng R5-920 QH301-705.5 Daisuke Suzuki verfasserin aut iPSC-Derived Platelets Depleted of HLA Class I Are Inert to Anti-HLA Class I and Natural Killer Cell Immunity 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: 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. : T cells and antibodies or NK cells reject HLA-I-incompatible or HLA-I-deficient cells, respectively. Sugimoto and colleagues produced HLA-I null platelets from iPSCs in a clinically applicable system and found that platelets can circulate even in human NK cell-reconstituted mice. Potentially, universal HLA-KO platelets could treat patients suffering from platelet transfusion refractoriness caused by HLA-I incompatibility. Keywords: platelet, megakaryocyte, iPSC, HLA class I, natural killer cell, regenerative medicine, imMKCL, platelet transfusion, refractoriness, MSTRG mice, IL-15 Medicine (General) Biology (General) Charlotte Flahou verfasserin aut Norihide Yoshikawa verfasserin aut Ieva Stirblyte verfasserin aut Yoshikazu Hayashi verfasserin aut Akira Sawaguchi verfasserin aut Marina Akasaka verfasserin aut Sou Nakamura verfasserin aut Natsumi Higashi verfasserin aut Huaigeng Xu verfasserin aut Takuya Matsumoto verfasserin aut Kosuke Fujio verfasserin aut Markus G. Manz verfasserin aut Akitsu Hotta verfasserin aut Hitoshi Takizawa verfasserin aut Koji Eto verfasserin aut Naoshi Sugimoto verfasserin aut In Stem Cell Reports Elsevier, 2015 14(2020), 1, Seite 49-59 (DE-627)749730862 (DE-600)2720528-9 22136711 nnns volume:14 year:2020 number:1 pages:49-59 https://doi.org/10.1016/j.stemcr.2019.11.011 kostenfrei https://doaj.org/article/9f437e1b02f6488582832358c907a1bf kostenfrei http://www.sciencedirect.com/science/article/pii/S221367111930414X kostenfrei https://doaj.org/toc/2213-6711 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 14 2020 1 49-59 |
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10.1016/j.stemcr.2019.11.011 doi (DE-627)DOAJ006555985 (DE-599)DOAJ9f437e1b02f6488582832358c907a1bf DE-627 ger DE-627 rakwb eng R5-920 QH301-705.5 Daisuke Suzuki verfasserin aut iPSC-Derived Platelets Depleted of HLA Class I Are Inert to Anti-HLA Class I and Natural Killer Cell Immunity 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: 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. : T cells and antibodies or NK cells reject HLA-I-incompatible or HLA-I-deficient cells, respectively. Sugimoto and colleagues produced HLA-I null platelets from iPSCs in a clinically applicable system and found that platelets can circulate even in human NK cell-reconstituted mice. Potentially, universal HLA-KO platelets could treat patients suffering from platelet transfusion refractoriness caused by HLA-I incompatibility. Keywords: platelet, megakaryocyte, iPSC, HLA class I, natural killer cell, regenerative medicine, imMKCL, platelet transfusion, refractoriness, MSTRG mice, IL-15 Medicine (General) Biology (General) Charlotte Flahou verfasserin aut Norihide Yoshikawa verfasserin aut Ieva Stirblyte verfasserin aut Yoshikazu Hayashi verfasserin aut Akira Sawaguchi verfasserin aut Marina Akasaka verfasserin aut Sou Nakamura verfasserin aut Natsumi Higashi verfasserin aut Huaigeng Xu verfasserin aut Takuya Matsumoto verfasserin aut Kosuke Fujio verfasserin aut Markus G. Manz verfasserin aut Akitsu Hotta verfasserin aut Hitoshi Takizawa verfasserin aut Koji Eto verfasserin aut Naoshi Sugimoto verfasserin aut In Stem Cell Reports Elsevier, 2015 14(2020), 1, Seite 49-59 (DE-627)749730862 (DE-600)2720528-9 22136711 nnns volume:14 year:2020 number:1 pages:49-59 https://doi.org/10.1016/j.stemcr.2019.11.011 kostenfrei https://doaj.org/article/9f437e1b02f6488582832358c907a1bf kostenfrei http://www.sciencedirect.com/science/article/pii/S221367111930414X kostenfrei https://doaj.org/toc/2213-6711 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 14 2020 1 49-59 |
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10.1016/j.stemcr.2019.11.011 doi (DE-627)DOAJ006555985 (DE-599)DOAJ9f437e1b02f6488582832358c907a1bf DE-627 ger DE-627 rakwb eng R5-920 QH301-705.5 Daisuke Suzuki verfasserin aut iPSC-Derived Platelets Depleted of HLA Class I Are Inert to Anti-HLA Class I and Natural Killer Cell Immunity 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: 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. : T cells and antibodies or NK cells reject HLA-I-incompatible or HLA-I-deficient cells, respectively. Sugimoto and colleagues produced HLA-I null platelets from iPSCs in a clinically applicable system and found that platelets can circulate even in human NK cell-reconstituted mice. Potentially, universal HLA-KO platelets could treat patients suffering from platelet transfusion refractoriness caused by HLA-I incompatibility. Keywords: platelet, megakaryocyte, iPSC, HLA class I, natural killer cell, regenerative medicine, imMKCL, platelet transfusion, refractoriness, MSTRG mice, IL-15 Medicine (General) Biology (General) Charlotte Flahou verfasserin aut Norihide Yoshikawa verfasserin aut Ieva Stirblyte verfasserin aut Yoshikazu Hayashi verfasserin aut Akira Sawaguchi verfasserin aut Marina Akasaka verfasserin aut Sou Nakamura verfasserin aut Natsumi Higashi verfasserin aut Huaigeng Xu verfasserin aut Takuya Matsumoto verfasserin aut Kosuke Fujio verfasserin aut Markus G. Manz verfasserin aut Akitsu Hotta verfasserin aut Hitoshi Takizawa verfasserin aut Koji Eto verfasserin aut Naoshi Sugimoto verfasserin aut In Stem Cell Reports Elsevier, 2015 14(2020), 1, Seite 49-59 (DE-627)749730862 (DE-600)2720528-9 22136711 nnns volume:14 year:2020 number:1 pages:49-59 https://doi.org/10.1016/j.stemcr.2019.11.011 kostenfrei https://doaj.org/article/9f437e1b02f6488582832358c907a1bf kostenfrei http://www.sciencedirect.com/science/article/pii/S221367111930414X kostenfrei https://doaj.org/toc/2213-6711 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 14 2020 1 49-59 |
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Daisuke Suzuki @@aut@@ Charlotte Flahou @@aut@@ Norihide Yoshikawa @@aut@@ Ieva Stirblyte @@aut@@ Yoshikazu Hayashi @@aut@@ Akira Sawaguchi @@aut@@ Marina Akasaka @@aut@@ Sou Nakamura @@aut@@ Natsumi Higashi @@aut@@ Huaigeng Xu @@aut@@ Takuya Matsumoto @@aut@@ Kosuke Fujio @@aut@@ Markus G. Manz @@aut@@ Akitsu Hotta @@aut@@ Hitoshi Takizawa @@aut@@ Koji Eto @@aut@@ Naoshi Sugimoto @@aut@@ |
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iPSC-Derived Platelets Depleted of HLA Class I Are Inert to Anti-HLA Class I and Natural Killer Cell Immunity |
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Daisuke Suzuki Charlotte Flahou Norihide Yoshikawa Ieva Stirblyte Yoshikazu Hayashi Akira Sawaguchi Marina Akasaka Sou Nakamura Natsumi Higashi Huaigeng Xu Takuya Matsumoto Kosuke Fujio Markus G. Manz Akitsu Hotta Hitoshi Takizawa Koji Eto Naoshi Sugimoto |
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ipsc-derived platelets depleted of hla class i are inert to anti-hla class i and natural killer cell immunity |
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iPSC-Derived Platelets Depleted of HLA Class I Are Inert to Anti-HLA Class I and Natural Killer Cell Immunity |
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Summary: 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. : T cells and antibodies or NK cells reject HLA-I-incompatible or HLA-I-deficient cells, respectively. Sugimoto and colleagues produced HLA-I null platelets from iPSCs in a clinically applicable system and found that platelets can circulate even in human NK cell-reconstituted mice. Potentially, universal HLA-KO platelets could treat patients suffering from platelet transfusion refractoriness caused by HLA-I incompatibility. Keywords: platelet, megakaryocyte, iPSC, HLA class I, natural killer cell, regenerative medicine, imMKCL, platelet transfusion, refractoriness, MSTRG mice, IL-15 |
abstractGer |
Summary: 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. : T cells and antibodies or NK cells reject HLA-I-incompatible or HLA-I-deficient cells, respectively. Sugimoto and colleagues produced HLA-I null platelets from iPSCs in a clinically applicable system and found that platelets can circulate even in human NK cell-reconstituted mice. Potentially, universal HLA-KO platelets could treat patients suffering from platelet transfusion refractoriness caused by HLA-I incompatibility. Keywords: platelet, megakaryocyte, iPSC, HLA class I, natural killer cell, regenerative medicine, imMKCL, platelet transfusion, refractoriness, MSTRG mice, IL-15 |
abstract_unstemmed |
Summary: 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. : T cells and antibodies or NK cells reject HLA-I-incompatible or HLA-I-deficient cells, respectively. Sugimoto and colleagues produced HLA-I null platelets from iPSCs in a clinically applicable system and found that platelets can circulate even in human NK cell-reconstituted mice. Potentially, universal HLA-KO platelets could treat patients suffering from platelet transfusion refractoriness caused by HLA-I incompatibility. Keywords: platelet, megakaryocyte, iPSC, HLA class I, natural killer cell, regenerative medicine, imMKCL, platelet transfusion, refractoriness, MSTRG mice, IL-15 |
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iPSC-Derived Platelets Depleted of HLA Class I Are Inert to Anti-HLA Class I and Natural Killer Cell Immunity |
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Charlotte Flahou Norihide Yoshikawa Ieva Stirblyte Yoshikazu Hayashi Akira Sawaguchi Marina Akasaka Sou Nakamura Natsumi Higashi Huaigeng Xu Takuya Matsumoto Kosuke Fujio Markus G. Manz Akitsu Hotta Hitoshi Takizawa Koji Eto Naoshi Sugimoto |
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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. : T cells and antibodies or NK cells reject HLA-I-incompatible or HLA-I-deficient cells, respectively. Sugimoto and colleagues produced HLA-I null platelets from iPSCs in a clinically applicable system and found that platelets can circulate even in human NK cell-reconstituted mice. Potentially, universal HLA-KO platelets could treat patients suffering from platelet transfusion refractoriness caused by HLA-I incompatibility. Keywords: platelet, megakaryocyte, iPSC, HLA class I, natural killer cell, regenerative medicine, imMKCL, platelet transfusion, refractoriness, MSTRG mice, IL-15</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine (General)</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Biology (General)</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Charlotte Flahou</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Norihide Yoshikawa</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ieva Stirblyte</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yoshikazu Hayashi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Akira Sawaguchi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Marina Akasaka</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sou Nakamura</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Natsumi Higashi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Huaigeng Xu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Takuya Matsumoto</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Kosuke Fujio</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Markus G. 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