At Tuesday’s State-of-the-Art Session, “Stem Cell Engineering”, Alessandra Balduini, M.D. presented her research on megakaryocyte matrix interactions and platelet production.
- She has developed a functional human organ/tissue model of the bone marrow designed to study megakaryocyte matrix interactions and platelet production ex vivo.
- This model will allow examination of mechanisms of platelet release, identification of platelet-related diseases, and identification of new therapeutic targets.
Megakaryocytes are rare cells found in the bone marrow, responsible for the production and release of millions of platelets into the bloodstream. This process, called megakaryopoiesis, occurs within the complex bone marrow microenvironment. The underlying relationships between megakaryocyte maturation and bone marrow components are key factors in this process. Bone marrow is structured as a tridimensional network of branching sinusoids surrounding islets of hemopoietic cells, immersed in a mesh of extracellular matrix and soluble/humoral factors. Megakaryocyte interactions with extracellular matrices via specific surface receptors regulate many functions, with biochemical mediators, physical parameters, and membrane elasticity as fundamental elements of the processes involved.
Despite their critical role, little is known regarding the mechanisms that control the developmental process of megakaryocytes and govern the production of platelets in the bone marrow.
To overcome these limitations, Balduini developed a functional human organ/tissue model of the bone marrow made of silk derived from cocoons. In order to mimic human bone marrow, she is functionalizing this biomaterial with different marrow components. There are challenges to overcome with the model, from successfully mimicking the physiological composition and function of bone marrow, to the generation and collection of the platelets that are produced, and the validation of their viability and function for human use.
The overall goal of this work is to develop a model that will be used to study mechanisms of platelet release, characterize diseases related to platelet production, and identify new therapeutic targets. This will be possible only by collaboration of researchers representing diverse areas of expertise in a multidisciplinary approach.