Turbulence activates platelet biogenesis to enable clinical scale ex vivo production

• Yukitaka Ito ^[1] ; Sou Nakamura ^[1] ; Naoshi Sugimoto ^[1]
  1. [1] Kyoto University

     Kyoto University

     Kamigyō-ku, Japón

     
• Localización: Cell, ISSN 0092-8674, Vol. 174, Nº. 3, 2018, págs. 636-648
• Idioma: inglés
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• Resumen

  • 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.