Engineering the Vascular Niche: Development of a Basement Membrane Model for Studying Megakaryopoiesis In Vitro

Thrombocytopenia occurs when a patient suffers from an abnormally low platelet count in the peripheral blood; usually a result of disease, trauma, or cancer treatment. To treat these patients, it is estimated that two million platelet transfusions are performed in the U.S. each year. This high demand for platelets has created a clinical demand for studying the causes of thrombocytopenia and alternative routes for treatment. Platelets are anuclear cells that are released into the bloodstream in the bone marrow by megakaryocytes (MKs) via the extension of long filaments called proplatelets. It is hypothesized that the vascular niche in the bone marrow, namely the basement membrane and vascular endothelium, plays a pivotal role in directing megakaryopoiesis. The goal of this project was to create a bone marrow basement membrane model that mimics the vascular niche for functional in vitro platelet production. We hypothesized that a silk film porous membrane with tunable material properties that resembles the physiologic basement membrane would support physiologic megakaryopoiesis.