OSTEOGENIC GROWTH PEPTIDE INCREASES BLOOD AND BONE-MARROW CELLULARITYAND ENHANCES ENGRAFTMENT OF BONE-MARROW TRANSPLANTS IN MICE

The osteogenic growth peptide (OGP) was characterized recently in rege nerating bone marrow (BM) and normal serum. In vitro, the OGP regulate s stromal-cell proliferation and differentiated functions. In vivo, an increase in serum OGP accompanies the osteogenic phase of postablatio n BM regeneration. The present results in normal mice show that OGP in duces a balanced increase in WBC counts and overall BM cellularity. In mice receiving myeloablative irradiation and syngeneic or semiallogen eic BM transplants, OGP stimulates hematopoietic reconstruction and do ubles the survival rate; these effects are dependent on initiating the OGP administration before irradiation. Chimerism measurements in semi allogeneic graft recipients suggest no preferential effect of OGP on r esidual host cells. The data implicate OGP in the acceleration of hema topoiesis secondary to expansion of the stromal microenvironment and/o r enhancement of stroma-derived signals to stem cells. The low-dose ef fectiveness of OGP is explained by the demonstration of an autocrine p ositive feedback loop that together with the OGP-binding protein susta ins high serum levels of the peptide. A potential OGP-based treatment in combination with chemoradiotherapy is attractive because of the OGP -induced balanced multilineage enhancement of hematopoiesis and possib le replacement of expensive recombinant cytokines by a readily synthes ized peptide. (C) 1996 by The American Society of Hematology.