Regulation of hematopoiesis in long term marrow cultures: role of humoral factors in the proliferation and differentiation of stem cells and committed progenitors.

Established systems of long-term bone marrow culture (LTBMC) have contributed to our understanding of the interrelationships between the adherent stromal cells and the stem cells, committed progenitors and mature terminally differentiated cells. While cell-mediated or short range stromal interactions appear to be a major source of homeostatic control between the stromal microenvironment and the stem cells, positive and negative humoral influences or long-range mechanisms also regulate stem cell proliferation and differentiation. Adherent stromal conditioned medium generates factors which can trigger CFU-s into DNA synthesis within 18 hours or inhibit incorporation of tritiated thymidine into rapidly proliferating CFU-s. Other adherent stromal factors reduce proliferation and terminal erythroid differentiation of BFU-e. Stromal cells also produce a synergistic activity which stimulates formation of giant macrophage colonies in conjunction with CSF. Continued examination of these factors should lead to better understanding of the mechanisms involved in control of hematopoietic stem cell proliferation and differentiation.