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Production and nonclinical evaluation of an autologous iPSC–derived platelet product for the iPLAT1 clinical trial

Donor-derived platelets are used to treat or prevent hemorrhage in patients with thrombocytopenia. However, ∼5% or more of these patients are complicated with alloimmune platelet transfusion refractoriness (allo-PTR) due to alloantibodies against HLA-I or human platelet antigens (HPA). In these case...

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Autores principales: Sugimoto, Naoshi, Nakamura, Sou, Shimizu, Shin, Shigemasa, Akiko, Kanda, Junya, Matsuyama, Nobuki, Tanaka, Mitsunobu, Hayashi, Tomoya, Fuchizaki, Akihiro, Nogawa, Masayuki, Watanabe, Naohide, Okamoto, Shinichiro, Handa, Makoto, Sawaguchi, Akira, Momose, Dai, Koh, Ki-Ryang, Tani, Yoshihiko, Takaori-Kondo, Akifumi, Eto, Koji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society of Hematology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9706535/
https://www.ncbi.nlm.nih.gov/pubmed/36149941
http://dx.doi.org/10.1182/bloodadvances.2022008512
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author Sugimoto, Naoshi
Nakamura, Sou
Shimizu, Shin
Shigemasa, Akiko
Kanda, Junya
Matsuyama, Nobuki
Tanaka, Mitsunobu
Hayashi, Tomoya
Fuchizaki, Akihiro
Nogawa, Masayuki
Watanabe, Naohide
Okamoto, Shinichiro
Handa, Makoto
Sawaguchi, Akira
Momose, Dai
Koh, Ki-Ryang
Tani, Yoshihiko
Takaori-Kondo, Akifumi
Eto, Koji
author_facet Sugimoto, Naoshi
Nakamura, Sou
Shimizu, Shin
Shigemasa, Akiko
Kanda, Junya
Matsuyama, Nobuki
Tanaka, Mitsunobu
Hayashi, Tomoya
Fuchizaki, Akihiro
Nogawa, Masayuki
Watanabe, Naohide
Okamoto, Shinichiro
Handa, Makoto
Sawaguchi, Akira
Momose, Dai
Koh, Ki-Ryang
Tani, Yoshihiko
Takaori-Kondo, Akifumi
Eto, Koji
author_sort Sugimoto, Naoshi
collection PubMed
description Donor-derived platelets are used to treat or prevent hemorrhage in patients with thrombocytopenia. However, ∼5% or more of these patients are complicated with alloimmune platelet transfusion refractoriness (allo-PTR) due to alloantibodies against HLA-I or human platelet antigens (HPA). In these cases, platelets from compatible donors are necessary, but it is difficult to find such donors for patients with rare HLA-I or HPA. To produce platelet products for patients with aplastic anemia with allo-PTR due to rare HPA-1 mismatch in Japan, we developed an ex vivo good manufacturing process (GMP)–based production system for an induced pluripotent stem cell–derived platelet product (iPSC-PLTs). Immortalized megakaryocyte progenitor cell lines (imMKCLs) were established from patient iPSCs, and a competent imMKCL clone was selected for the master cell bank (MCB) and confirmed for safety, including negativity of pathogens. From this MCB, iPSC-PLTs were produced using turbulent flow bioreactors and new drugs. In extensive nonclinical studies, iPSC-PLTs were confirmed for quality, safety, and efficacy, including hemostasis in a rabbit model. This report presents a complete system for the GMP-based production of iPSC-PLTs and the required nonclinical studies and thus supports the iPLAT1 study, the first-in-human clinical trial of iPSC-PLTs in a patient with allo-PTR and no compatible donor using the autologous product. It also serves as a comprehensive reference for the development of widely applicable allogeneic iPSC-PLTs and other cell products that use iPSC-derived progenitor cells as MCB.
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spelling pubmed-97065352022-11-30 Production and nonclinical evaluation of an autologous iPSC–derived platelet product for the iPLAT1 clinical trial Sugimoto, Naoshi Nakamura, Sou Shimizu, Shin Shigemasa, Akiko Kanda, Junya Matsuyama, Nobuki Tanaka, Mitsunobu Hayashi, Tomoya Fuchizaki, Akihiro Nogawa, Masayuki Watanabe, Naohide Okamoto, Shinichiro Handa, Makoto Sawaguchi, Akira Momose, Dai Koh, Ki-Ryang Tani, Yoshihiko Takaori-Kondo, Akifumi Eto, Koji Blood Adv Regular Article Donor-derived platelets are used to treat or prevent hemorrhage in patients with thrombocytopenia. However, ∼5% or more of these patients are complicated with alloimmune platelet transfusion refractoriness (allo-PTR) due to alloantibodies against HLA-I or human platelet antigens (HPA). In these cases, platelets from compatible donors are necessary, but it is difficult to find such donors for patients with rare HLA-I or HPA. To produce platelet products for patients with aplastic anemia with allo-PTR due to rare HPA-1 mismatch in Japan, we developed an ex vivo good manufacturing process (GMP)–based production system for an induced pluripotent stem cell–derived platelet product (iPSC-PLTs). Immortalized megakaryocyte progenitor cell lines (imMKCLs) were established from patient iPSCs, and a competent imMKCL clone was selected for the master cell bank (MCB) and confirmed for safety, including negativity of pathogens. From this MCB, iPSC-PLTs were produced using turbulent flow bioreactors and new drugs. In extensive nonclinical studies, iPSC-PLTs were confirmed for quality, safety, and efficacy, including hemostasis in a rabbit model. This report presents a complete system for the GMP-based production of iPSC-PLTs and the required nonclinical studies and thus supports the iPLAT1 study, the first-in-human clinical trial of iPSC-PLTs in a patient with allo-PTR and no compatible donor using the autologous product. It also serves as a comprehensive reference for the development of widely applicable allogeneic iPSC-PLTs and other cell products that use iPSC-derived progenitor cells as MCB. The American Society of Hematology 2022-09-28 /pmc/articles/PMC9706535/ /pubmed/36149941 http://dx.doi.org/10.1182/bloodadvances.2022008512 Text en © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Regular Article
Sugimoto, Naoshi
Nakamura, Sou
Shimizu, Shin
Shigemasa, Akiko
Kanda, Junya
Matsuyama, Nobuki
Tanaka, Mitsunobu
Hayashi, Tomoya
Fuchizaki, Akihiro
Nogawa, Masayuki
Watanabe, Naohide
Okamoto, Shinichiro
Handa, Makoto
Sawaguchi, Akira
Momose, Dai
Koh, Ki-Ryang
Tani, Yoshihiko
Takaori-Kondo, Akifumi
Eto, Koji
Production and nonclinical evaluation of an autologous iPSC–derived platelet product for the iPLAT1 clinical trial
title Production and nonclinical evaluation of an autologous iPSC–derived platelet product for the iPLAT1 clinical trial
title_full Production and nonclinical evaluation of an autologous iPSC–derived platelet product for the iPLAT1 clinical trial
title_fullStr Production and nonclinical evaluation of an autologous iPSC–derived platelet product for the iPLAT1 clinical trial
title_full_unstemmed Production and nonclinical evaluation of an autologous iPSC–derived platelet product for the iPLAT1 clinical trial
title_short Production and nonclinical evaluation of an autologous iPSC–derived platelet product for the iPLAT1 clinical trial
title_sort production and nonclinical evaluation of an autologous ipsc–derived platelet product for the iplat1 clinical trial
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9706535/
https://www.ncbi.nlm.nih.gov/pubmed/36149941
http://dx.doi.org/10.1182/bloodadvances.2022008512
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