RRC ID 53865
著者 Ito Y, Nakamura S, Sugimoto N, Shigemori T, Kato Y, Ohno M, Sakuma S, Ito K, Kumon H, Hirose H, Okamoto H, Nogawa M, Iwasaki M, Kihara S, Fujio K, Matsumoto T, Higashi N, Hashimoto K, Sawaguchi A, Harimoto KI, Nakagawa M, Yamamoto T, Handa M, Watanabe N, Nishi E, Arai F, Nishimura S, Eto K.
タイトル Turbulence Activates Platelet Biogenesis to Enable Clinical Scale Ex Vivo Production.
ジャーナル Cell
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.
巻・号 174(3)
ページ 636-648.e18
公開日 2018-7-26
DOI 10.1016/j.cell.2018.06.011
PII S0092-8674(18)30736-0
PMID 30017246
MeSH Bioreactors Blood Platelets / metabolism* Cell Culture Techniques / instrumentation Cell Culture Techniques / methods* Humans Hydrodynamics Induced Pluripotent Stem Cells / metabolism Megakaryocytes / metabolism Megakaryocytes / physiology Thrombopoiesis / physiology*
IF 38.637
引用数 54
リソース情報
ヒト・動物細胞 10T1/2(RCB0247)