The regulation of hematopoietic growth factor production from cord mononuclear cells and its effect on newborn rat hematopoiesis

Abstract

Newborns are characterized by significant developmental immaturities in hematopoiesis and phagocytic immunity. Defects in myelopoiesis and thrombopoiesis predispose newborns to peripheral cytopenias, especially during states of increased demand. However, committed myeloid (CFU-GM) and megakaryocytic (CFU-Meg) progenitor cells in circulating cord blood are increased compared to that of adult bone marrow and/or adult peripheral blood. This increase in hematopoietic committed progenitor cells has allowed the use of cord blood for hematopoietic reconstitution following myeloablative therapy in transplantation. Decreased production of GM-CSF, G-CSF, and IL-3 has been demonstrated in cord-versus-adult mononuclear cells with a similar decrease in their mRNA transcript expression. Other growth factors, however, including steel factor, are increased in the basal state and further increased during stimulation from umbilical-vein endothelial cells versus adult-aortic endothelial cells. The use of single, sequential, or simultaneous administration of both early- and late-acting hematopoietic growth factors, however, has profound effects in the modulation of neonatal-rat hematopoiesis. The combination of G-CSF and early-acting CSFs, such as steel factor or IL-3, induces a significant increase in peripheral neutrophilia and bone marrow progenitor pools.