bone marrow osteoblastic niche a new model to study physiological regulation of megakaryopoiesis骨髓成骨细胞的利基市场一个新的模型来研究生理megakaryopoiesis监管.pdfVIP

Bone Marrow Osteoblastic Niche: A New Model to Study Physiological Regulation of Megakaryopoiesis 1,2 1 1 1 1,2 Isabella Pallotta , Michael Lovett , William Rice , David L. Kaplan *, Alessandra Balduini * 1 Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, United States of America, 2 Department of Biochemistry, University of Pavia, Pavia, Italy Abstract Background: The mechanism by which megakaryocytes (Mks) proliferate, differentiate, and release platelets into circulation are not well understood. Growing evidence indicates that a complex regulatory mechanism, involving cellular interactions, composition of the extracellular matrix and physical parameters such as oxygen tension, may contribute to the quiescent or permissive microenvironment related to Mk differentiation and maturation within the bone marrow. Methodology/Principal Findings: Differentiating human mesenchymal stem cells (hMSCs) into osteoblasts (hOSTs), we established an in vitro model for the osteoblastic niche. We demonstrated for the first time that the combination of HSCs, Mks and hypoxia sustain and promote bone formation by increasing type I collagen release from hOSTs and enhancing its fibrillar organization, as revealed by second harmonic generation microscopy. Through co-culture, we demonstrated that direct cell-cell contact modulates Mk maturation and differentiation. In particular we showed that low oxygen tension and direct interaction of hematopoietic stem cells (HSCs) with hOSTs inhibits Mk maturation and proplatelet formation (PPF). This regulatory mechanism was dependent on the fibrillar structure of type I collagen released by hOSTs and on the res