Cell · 2018
Turbulence Activates Platelet Biogenesis to Enable Clinical Scale Ex Vivo Production.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.