Mesenchymal Cells

The bone marrow (BM) stroma contains a heterogeneous population of cells, including endothelial cells, fibroblasts, adipocytes and osteogenic cells, and it was initially thought to function primarily as a structural framework upon which hematopoiesis occurs. Later evidence demonstrated, however, that at least two distinct stem cell populations reside in the bone marrow of many mammalian species: hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs), with the latter responsible for the maintenance of the non-hematopoietic bone marrow cells. MSCs, also termed multipotent marrow stromal cells or mesenchymal stromal cells, are a heterogeneous population of plastic-adherent, fibroblast-like cells, which can self-renew and differentiate into bone, adipose and cartilage tissue in culture. In the late 1960s, Friedenstein and colleagues established that single cell suspensions of BM stroma could generate colonies of adherent fibroblast-like cells in vitro. These colony-forming unitfibroblasts (CFU-Fs) were capable of osteogenic differentiation and provided the first evidence of a clonogenic precursor for cells of the bone lineage. The CFU-F assay is now widely used as a functional method to quantify stromal progenitors. Functional in vitro characterization of the stromal compartment by Dexter et al. in the 1970s then revealed its importance in regulating the proliferation, differentiation and survival of HSCs. CFU-F initiating cells in vivo have been shown to be quiescent, existing at a low frequency in human bone marrow.