Overall, the proposed project will integrate the observations of megakaryocyte subpopulations and enhanced platelet production in vivo. The overarching goal of this proposal is to identify molecular and environmental drivers of the platelet producing megakaryocytes subpopulation. These observations will pave way for improved protocols for in vitro platelet generation that eventually will be implemented for large scale production of platelets in bioreactors. The development of such protocols will lead to tailored personalized approaches based on in vitro generation of platelet concentrates for clinical use.
Furthermore, improved understanding of these fundamental hematopoietic processes can advance studies to enhance thrombopoiesis in vivo.
With this study, the LSBR will contribute to a better overall understanding of megakaryopoiesis and thrombopoiesis in the complexity of the bone marrow. This knowledge will have future implications for the overarching aim of myself and Sanquin to therapeutically (re)-programming megakaryocytes for more efficient platelet generation in vitro for transfusion purposes. In addition to an alternative for donor derived platelets, in vitro generated platelets hold prospective to be loaded with specific proteins for therapeutic applications. Furthermore, improved understanding of these fundamental hematopoietic processes can advance studies to enhance thrombopoiesis in vivo as a therapy for chemotherapy or surgery induced thrombocytopenia.