Bone Marrow Stroma
The bone marrow forms a suitable environment for stem cell survival, self‐renewal and formation of differentiated progenitor cells. It is composed of stromal cells and a microvascular network (Fig. 1.4). The stromal cells include mesenchymal stem cells, adipocytes, fibroblasts, osteoblasts, endothelial cells and macrophages and they secrete extracellular molecules such as collagen, glycoproteins (fibronectin and thrombospondin) and glycosaminoglycans (hyaluronic acid and chondroitin derivatives) to form an extracellular matrix. In addition, stromal cells secrete several growth factors necessary for stem cell survival.
Mesenchymal stem cells are critical in stromal cell formation. Together with osteoblasts or endothelial cells they form niches and provide the growth factors, adhesion molecules and cytokines which support stem cells, e.g. the protein jagged, on stromal cells, binds to a receptor NOTCH1 on stem cells which then becomes a transcription factor involved in the cell cycle.
Stem cells are able to traffic around the body and are found in peripheral blood in low numbers. In order to exit the bone marrow, cells must cross the blood vessel endothelium and this process of mobilization is enhanced by administration of growth factors such as granulocyte colony‐stimulating factor (G‐CSF) (see p. 91). The reverse process of stem cell homing appears to depend on a chemokine gradient in which the stromal‐derived factor 1 (SDF‐1) which binds to its receptor CXCR4 on HSC is critical. Several critical interactions maintain stem cell viability and production in the stroma including stem cell factor (SCF) and jagged proteins expressed on stroma and their respective receptors KIT and NOTCH expressed on stem cells.