[PDF][PDF] Turbulence activates platelet biogenesis to enable clinical scale ex vivo production

Y Ito, S Nakamura, N Sugimoto, T Shigemori, Y Kato… - Cell, 2018 - cell.com
Y Ito, S Nakamura, N Sugimoto, T Shigemori, Y Kato, M Ohno, S Sakuma, K Ito, H Kumon
Cell, 2018cell.com
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 …
Summary
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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