Integrated Biophysical and Biochemical Signals Augment Megakaryopoiesis and Thrombopoiesis in a Three-Dimensional Rotary Culture System.

Platelet transfusion has been widely used in patients undergoing chemotherapy or radiotherapy; however, the shortage of the platelet supply limits the care of patients. Although derivation of clinical-scale platelets in vitro could provide a new source for transfusion, the devices and procedures for deriving scalable platelets for clinical applications have not been established. In the present study, we found that a rotary cell culture system (RCCS) can potentiate megakaryopoiesis and significantly improve the efficiency of platelet generation. When used with chemical compounds and growth factors identified via small-scale screening, the RCCS improved platelet generation efficiency by as much as ∼3.7-fold compared with static conditions. Shear force, simulated microgravity, and better diffusion of nutrients and oxygen from the RCCS, altogether, might account for the improved efficient platelet generation. The cost-effective and highly controllable strategy and methodology represent an important step toward large-scale platelet production for future biomedical and clinical applications. Significance: Platelet transfusion has been widely used in patients undergoing chemotherapy or radiotherapy; however, the shortage of platelet supply limits the care of patients. Thus, derivation of clinical-scale platelets in vitro would provide a new source for transfusion. The present study evaluated a rotary suspension cell culture system that was able to potentiate megakaryopoiesis and significantly improved the efficiency of platelet generation. When used with chemical compounds and growth factors identified via small-scale screening, the three-dimensional system improved platelet generation efficiency compared with the static condition. The three-dimensional device and the strategy developed in the present study should markedly improve the generation of large-scale platelets for use in future biomedical and clinical settings.

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