Sources of haemopoietic stem cell proliferation: stimulators and inhibitors

Based on earlier findings that haemopoietic tissue contains extractable factors which are capable of specifically inhibiting or stimulating the movement of CFU-S into DNA synthesis, a series of preliminary experiments has now been carried out to investigate their cellular source(s), their activity in vivo, and their applicability to human problems. In vivo treatment of mice, in which femoral CFU-S are proliferating rapidly, with the inhibitory factor reduces the proportion of CFU-S in DNA synthesis to non-significant proportions. In addition, the inhibitor is capable of reducing the number of CFU-S induced to enter S following treatment with hydroxyurea, thus protecting CFU-S from the lethal effects of S-phase cytotoxic agents. Removal of specific types of marrow cells shows that both inhibitor and stimulator are adherent, phagocytic and, in the case of inhibitor, Thy--1-. These results suggest that the producer cells probably reside somewhere in the heterogeneous macrophage complex though their different densities suggest they are probably different cell types. Fresh human bone marrow is found to contain a very similar inhibitor and long-term cultures are also found to produce it continuously. The isolation of the producer cells may thus contribute to the understanding of normal physiological stem cell regulation and, by in vivo application, its eventual manipulation and protection.