Uniform impact on individual megakaryocytes is essential for efficient in vitro platelet production

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Abstract
Different approaches are being developed to efficiently produce in vitro platelets from cultured megakaryocytes to meet the constant demand of platelet transfusion and serve for research purposes. Recent works have shown that turbulence and periodic stress can significantly enhance platelet yield. Here we have developed and characterized a platelet production device that takes in account these properties. This device is based on the Taylor-Couette reactor in which a suspension is confined and sheared between two concentric cylinders. We have demonstrated that such a system allows obtaining high number of in vitro platelets per megakaryocyte with native-like morphology and functional properties. Using the combination of in silico and in vitro techniques, we claimed that overall turbulent conditions are not sufficient for efficient platelet release, and highlighted the importance of the uniform impact of flow on each megakaryocyte, a property that must be taken into account along with general flow characteristics when designing platelet release bioreactors. In addition, we have demonstrated that our system can be scaled up to large volumes without loss of efficiency, a significant advantage for the industrialization of platelet culture. In conclusion, we have developed a platelet production device with a predictable and highly precise effect on each megakaryocyte.

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