Osteogenic growth peptide increases blood and bone marrow cellularity and enhances engraftment of bone marrow transplants in mice.
The osteogenic growth peptide (OGP) was characterized recently in regenerating bone marrow (BM) and normal serum. In vitro, the OGP regulates stromal-cell proliferation and differentiated functions. In vivo, an increase in serum OGP accompanies the osteogenic phase of postablation BM regeneration. The present results in normal mice show that OGP induces a balanced increase in WBC counts and overall BM cellularity. In mice receiving myeloablative irradiation and syngeneic or semiallogeneic BM transplants, OGP stimulates hematopoietic reconstruction and doubles the survival rate; these effects are dependent on initiating the OGP administration before irradiation. Chimerism measurements in semiallogeneic graft recipients suggest no preferential effect of OGP on residual host cells. The data implicate OGP in the acceleration of hematopoiesis secondary to expansion of the stromal microenvironment and/or enhancement of stroma-derived signals to stem cells. The low-dose effectiveness of OGP is explained by the demonstration of an autocrine positive feedback loop that together with the OGP-binding protein sustains high serum levels of the peptide. A potential OGP-based treatment in combination with chemoradiotherapy is attractive because of the OGP-induced balanced multi-lineage enhancement of hematopoiesis and possible replacement of expensive recombinant cytokines by a readily synthesized peptide.
Gurevitch
O
O
Department of Bone Marrow Transplantation and Cancer/Immunobiology Research Laboratory, Hadassah-Hebrew University Hospital, Jerusalem, Israel.
Slavin
S
S
Muhlrad
A
A
Shteyer
A
A
Gazit
D
D
Chorev
M
M
Vidson
M
M
Namdar-Attar
M
M
Berger
E
E
Bleiberg
I
I
Bab
I
I
D000818:Animals; D001773:Blood Cells / Q000187:drug effects*; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology* / Q000502:physiology*; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects; D006657:Histones; D007279:Injections, Subcutaneous; D036341:Intercellular Signaling Peptides and Proteins; D007958:Leukocyte Count / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000494:pharmacology* / Q000502:physiology*
D006133:Growth Substances; D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C074533:osteogenic growth peptide