Hepatocyte growth factor is secreted by osteoblasts and cooperatively permits the survival of haematopoietic progenitors.

Human osteoblasts (HOBs) support the growth of human haematopoietic progenitor cells, and support the survival and limited expansion of long-term culture-initiating cells. Using human CD34+ cells and the murine myelomonocytic cell line NFS-60 as targets, we previously found that one component of HOB-derived haematopoietic activity is cell-associated granulocyte colony-stimulating factor (G-CSF). However, antibody failed to neutralize all the activity, suggesting that more than one factor supports haematopoietic cells. In the present investigations, we asked whether the HOB-derived, non-G-CSF secreted activity was as a result of other known growth factors. We found that, among the cytokines expressed by HOBs, only hepatocyte growth factor (HGF) and G-CSF stimulated NFS-60 cell proliferation. HOB cells and osteosarcoma cells secreted biologically active HGF, although the levels varied considerably. Moreover, addition of neutralizing HGF antibody to CD34+ cell/HOB co-cultures resulted in a significant reduction ( approximately 50%) in the ability of the HOBs to support haematopoietic progenitor cells. These results suggest that a major component of osteoblast-derived haematopoietic activity is HGF. Secretion of HGF, in concert with cell-associated cytokines such as G-CSF, may account for the stem cell-stimulating activities of osteogenic cells and, thereby, the unique stem cell-supporting role of the osteoblasts within the bone marrow microenvironment.