The role of colony stimulating factors, interleukin 1 and stromal extracellular matrix in the regulation of stem cell development.

Abstract

In recent years increasing attention has been paid to elucidating the way in which stem cell development is regulated. There have been essentially two in vitro approaches to the problem. In the first approach, haemopoietic stem cells have been cultured on adherent bone marrow stroma (long-term bone marrow culture): this has revealed the importance of stromal-stem cell interactions. In the second approach haemopoietic cells have been cultured in short-term clonogenic systems: this has shown the importance of a group of growth factors, the colony stimulating factors (CSFs). Work carried out by our group has provided a link between these two systems, as heparan sulphate a component of the stromal extra-cellular matrix is able to bind CSFs and present them to the stem cells in an active form. Furthermore, we have shown that synergistic interactions between combinations of CSFs, or between CSFs and IL-1 have a potentially critical role to play in stem cell development, due to their ability to stimulate a proportion of IL-3 responsive, multi-potential cells. This provides a possible explanation for the growth and development of stem cells in association with stromal cells in the apparent absence of IL-3 production by stroma.