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Turbulence Activates Platelet Biogenesis to Enable Clinical Scale Ex Vivo Production.
Ito, Yukitaka; Nakamura, Sou; Sugimoto, Naoshi; Shigemori, Tomohiro; Kato, Yoshikazu; Ohno, Mikiko; Sakuma, Shinya; Ito, Keitaro; Kumon, Hiroki; Hirose, Hidenori; Okamoto, Haruki; Nogawa, Masayuki; Iwasaki, Mio; Kihara, Shunsuke; Fujio, Kosuke; Matsumoto, Takuya; Higashi, Natsumi; Hashimoto, Kazuya; Sawaguchi, Akira; Harimoto, Ken-Ichi; Nakagawa, Masato; Yamamoto, Takuya; Handa, Makoto; Watanabe, Naohide; Nishi, Eiichiro; Arai, Fumihito; Nishimura, Satoshi; Eto, Koji.
Afiliação
  • Ito Y; Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan; Kyoto Development Center, Megakaryon Corporation, Kyoto, Japan.
  • Nakamura S; Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
  • Sugimoto N; Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
  • Shigemori T; Kyoto Development Center, Megakaryon Corporation, Kyoto, Japan.
  • Kato Y; Mixing Technology Laboratory, SATAKE Chemical Equipment Manufacturing Ltd., Saitama, Japan.
  • Ohno M; Department of Pharmacology, Shiga University of Medical Science, Otsu, Japan.
  • Sakuma S; Department of Micro-Nano Systems Engineering, Nagoya University, Nagoya, Japan.
  • Ito K; Department of Micro-Nano Systems Engineering, Nagoya University, Nagoya, Japan.
  • Kumon H; Department of Micro-Nano Systems Engineering, Nagoya University, Nagoya, Japan.
  • Hirose H; Kyoto Development Center, Megakaryon Corporation, Kyoto, Japan.
  • Okamoto H; Kyoto Development Center, Megakaryon Corporation, Kyoto, Japan.
  • Nogawa M; Center for Transfusion Medicine and Cell Therapy, Keio University School of Medicine, Tokyo, Japan.
  • Iwasaki M; Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
  • Kihara S; Department of Fundamental Cell Technology, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
  • Fujio K; Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
  • Matsumoto T; Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
  • Higashi N; Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
  • Hashimoto K; Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
  • Sawaguchi A; Department of Anatomy, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
  • Harimoto KI; Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
  • Nakagawa M; Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
  • Yamamoto T; Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan; AMED-CREST, AMED, Tokyo, Japan.
  • Handa M; Center for Transfusion Medicine and Cell Therapy, Keio University School of Medicine, Tokyo, Japan.
  • Watanabe N; Center for Transfusion Medicine and Cell Therapy, Keio University School of Medicine, Tokyo, Japan.
  • Nishi E; Department of Pharmacology, Shiga University of Medical Science, Otsu, Japan.
  • Arai F; Department of Micro-Nano Systems Engineering, Nagoya University, Nagoya, Japan.
  • Nishimura S; Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
  • Eto K; Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan; Department of Regenerative Medicine, Chiba University Graduate School of Medicine, Chiba, Japan. Electronic address: kojieto@cira.kyoto-u.ac.jp.
Cell ; 174(3): 636-648.e18, 2018 07 26.
Article em En | MEDLINE | ID: mdl-30017246
ABSTRACT
The ex vivo generation of platelets from human-induced pluripotent cells (hiPSCs) is expected to compensate donor-dependent transfusion systems. However, manufacturing the clinically required number of platelets remains unachieved due to the low platelet release from hiPSC-derived megakaryocytes (hiPSC-MKs). Here, we report turbulence as a physical regulator in thrombopoiesis in vivo and its application to turbulence-controllable bioreactors. The identification of turbulent energy as a determinant parameter allowed scale-up to 8 L for the generation of 100 billion-order platelets from hiPSC-MKs, which satisfies clinical requirements. Turbulent flow promoted the release from megakaryocytes of IGFBP2, MIF, and Nardilysin to facilitate platelet shedding. hiPSC-platelets showed properties of bona fide human platelets, including circulation and hemostasis capacities upon transfusion in two animal models. This study provides a concept in which a coordinated physico-chemical mechanism promotes platelet biogenesis and an innovative strategy for ex vivo platelet manufacturing.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Plaquetas / Técnicas de Cultura de Células / Trombopoese Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Japão
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Plaquetas / Técnicas de Cultura de Células / Trombopoese Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Japão