Insulin-like Growth Factors Stimulate Erythropoiesis in Serum-substituted Umbilical Cord Blood Cultures

The stimulatory effects of the insulin-like growth factors (IGFs) on erythroid colony formation by hematopoietic progenitor cells derived from adult bone marrow and peripheral blood have been well demonstrated. To enhance our understanding of the potential role of IGFs in human newborn erythropoiesis, we studied the effects of IGF-I and IGF-II on neonatal erythropoiesis in vitro. Erythroid progenitor cells were recovered from umbilical cord blood collected at scheduled Cesarean sections from women with term, uncomplicated pregnancies. Light-density cord blood mononuclear cells were cultured for 7 days in a serum-substituted culture system supplemented with and without purified human recombinant erythropoietin (0.5 to 2.0 U/mL) and recombinant human IGFs. Addition of IGF-I (1 to 100 ng/mL) resulted in up to a 4-fold increase over baseline erythropoietin-dependent colony formation at 7 days with a maximal effect at 10 ng/mL. While subphysiologic doses of IGF-II caused a modest stimulation of erythropoiesis, addition of a physiologic concentration (100 ng/mL) resulted in up to a 4-fold enhancement in erythroid colony formation. This stimulatory effect persisted in cultures of mononuclear cells that were depleted of monocytes, myeloid cells, T cells and B cells prior to culture, suggesting that enhancement is the result of a direct IGF effect on progenitor cells. Addition of IGFs in the absence of erythropoietin resulted in erythroid colony formation in some but not all experiments. Whereas IGF-I was the primary regulator of erythropoietin-independent erythroid colony formation by adult erythroid progenitors, IGF-II was the predominant regulator of erythropoietin-independent erythroid colony formation by neonatal progenitor cells. We conclude that IGFs in physiologic doses directly stimulate neonatal cord blood erythroid progenitor cells and may play a role in developmental control of human erythropoiesis.