Growth and development of haemopoietic cells: a deterministic process?
The in vitro methods used to study haemopoiesis fall into two distinct categories. Short-term colony forming assays have identified a number of potent soluble factors capable of maintaining survival, proliferation and differentiation of haemopoietic cells but not their self-renewal. In contrast, in long-term bone marrow culture, extensive self-renewal occurs in the absence of exogenous factors and direct physical contact between haemopoietic cells and cells of the adherent stromal layer seems to be important. Obviously, LTBMC more closely resembles the situation in haemopoietic tissues but the potency of growth factors imply that they too play a role. Our data suggest that this may be at an earlier stage of haemopoietic development than previously appreciated. Primitive multipotent cells have the potential to respond to CSFs which were previously thought to stimulate only committed progenitor cells. This response is only seen, however, when the cells are exposed to a combination of factors which include either IL-1 or G-CSF. Thus, a combination of factors is able to recruit cells which are not already committed and determine the lineage along which they will differentiate. While it remains to be conclusively demonstrated that growth factors regulate normal "steady state" haemopoiesis in vivo it is clear that contact with stromal cells is important. The mechanisms by which the adherent layer influences haemopoietic development, however, are less obvious. We have shown that a component of stroma, heparan sulphate, is able to bind growth factors and present them to haemopoietic cells in a way that stimulates haemopoiesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Daniel
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CP
Department of Experimental Haematology, Paterson Institute for Cancer Research, Manchester, UK.
Ponting
I L
IL
Dexter
T M
TM
D000818:Animals; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology*
D003115:Colony-Stimulating Factors