INTRODUCTION
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The bone marrow niche is managed by an intricate regulatory network which include mesenchymal stem cells (MSCs), cytokines/growth factors, mature immune cells, Hematopoietic Stem and Progenitor Cells (HSPCs), and the extracellular matrix (ECM)
The ECM is a complex network of collagen and non-collagenous proteins that aid in the mechanical structure of the bone marrow and provides signals for cell differentiation
The ECM is essential for the regulation of hematopoiesis, the process by which blood cells are formed
Mesenchymal Stem Cells (MSCs)
Mesenchymal Stem Cells (MSCs) differentiate into three main cell types of the body: bone (osteocytes), cartilage (chondrocytes), and fat (adipocytes)
Hematopoietic Stem Cells (HSCs)
Hematopoietic stem cells (HSCs), on the other hand, are responsible for the formation of blood cells, including red blood cells, platelets, and white blood/immune cells
Osteogenesis & Aging
As the body ages, the balance of MSC differentiation shifts, with an increased tendency toward adipogenesis, while the function of HSCs decline
Though the function of HSCs declines, the transition from osteogenic to adipogenic development is associated with the tendency of HSPCs (Hematopoietic Stem and Progenitor Cells) to shift towards the myeloid lineage of immune cells
The shift in the bone marrow (BM) niche leads to the upregulation of adipogenic signals, increasing fat accumulation, and a decrease in bone mineral density
Central Questions
(1) How does the BM ECM affect hematopoiesis?
(2) Is the ECM's influence on HSCs due to a functional or phenotypic change?
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