The relative spatial distribution of in vitro-CFCs in the bone marrow, responding to specific growth factors

Haemopoietic progenitor cells are stimulated by a range of growth factors which promote colony growth in culture. The progenitors are a part of an age-structured developmental hierarchy in the tissue. The growth factors, although overlapping in their effects, stimulate cells preferentially at different stages in this programme. Femoral bone marrow was fractionated into axial (close to the central venous sinus) and marginal (close to the bone surface) cells. Progenitors which responded to IL-3, GM-CSF, G-CSF, M-CSF and SCF were then assayed in soft agar cultures. Consequent plots of their spatial distributions showed that the more primitive cells in vitro (responding to IL-3) were concentrated close to the bone surface. The peak concentrations of cells responding primarily to growth factors with progressively more affinity to more mature progenitor cells correspondingly appeared progressively further from the bone surface and closer to the point of release at the central venous sinus. This suggests that the developmental/maturational process in haemopoiesis is accompanied by a progressive movement of cells from the bone surface towards the central axial regions of the bone cavities. The most primitive cells are however exposed, close to the centre of the cavity, by a combination of SCF and G-CSF (or by a 50-fold increase in G-CSF concentration alone). These results corroborate earlier data which indicate a developmental movement of cells from the centre of the marrow tissue towards the bone surface and back again, sequentially encountering a series of growth factors which promote their differentiation into mature cells, for release at the central venous sinus.