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.
