Impact of the Megakaryocytic Vascular Niche on Platelet Biogenesis

The biogenesis of blood platelets is a process referred to as thrombopoiesis. Platelets are derived from large precursor cells residing in the bone marrow and are designated megakaryocytes. Mature megakaryocytes are mostly located juxtaposed to bone marrow sinusoids where they release long protrusions across the endothelial barrier into the blood stream where the final platelet biogenesis and sizing occurs. So far, it has remained unclear how bone marrow matrix proteins and cell-cell contacts at the endothelial influence the maturation, migration and terminal differentiation of megakaryocytes and prevent premature platelet release into the bone marrow cavity. Here, we provide the current concepts of a vascular niche for megakaryocytes and discuss relevant components of the microenvironment for platelet biogenesis. This includes matrix proteins fibronectin, vitronectin, collagens, and laminins and their receptors. In addition, we discuss the impact of chemokines, diffusable gases and lipids as well as altered conditions in extramedullary thrombopoiesis and malignancy. Finally, we discuss how platelet bioreactors can mimick this process to study the underlying mechanisms ex vivo.