Synergistic interactions in haemopoiesis: biological implications and clinical use.

Abstract

Growth factors promote the survival and proliferation of haemopoietic stem and progenitor cells, and in their absence the haemopoietic cells undergo apoptosis and die. The results of studies reported here indicate that multipotent stem cells have receptors for most, if not all, of the growth factors, but that even saturated binding of the receptors for a single growth factor is not sufficient to transduce an effective stimulus for the proliferation of these cells (possibly due to very low receptor numbers). However, when the growth factors are combined synergistic effects can be seen. Studies in which stem cell factor was used in combination with other growth factors showed that stem cell factor allowed the survival of stem cells, while a second growth factor (granulocyte-macrophage colony-stimulating factor) stimulated the stem cells to develop normally. Stem cell factor was also shown to alter the dose-response relationships of developing haemopoietic cells for other growth factors.