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

Human osteoblasts (HOBs) support the growth of human haematopoietic progeni tor cells, and support the survival and limited expansion of long-term cult ure-initiating cells. Using human CD34(+) cells and the murine myelomonocyt ic cell line NFS-60 as targets, we previously found that one component of H OB-derived haematopoietic activity is cell-associated granulocyte colony-st imulating factor (G-CSF). However, antibody failed to neutralize all the ac tivity, 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 osteosa rcoma cells secreted biologically active HGF, although the levels varied co nsiderably. Moreover, addition of neutralizing HGF antibody to CD34(+) cell /HOB co-cultures resulted in a significant reduction (approximate to 50%) i n the ability of the HOBs to support haematopoietic progenitor cells. These results suggest that a major component of osteoblast-derived haematopoieti c activity is HGF. Secretion of HGF, in concert with cell-associated cytoki nes 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.