Administration of recombinant human stem cell factor (rhSCF) and granulocyte-colony stimulating factor (rhG-CSF) to maternal and fetal rhesus monkeys(Macaca mulatta)

Studies with recombinant human stem cell factor (rhSCF) and granulocyte-col ony stimulating factor (rhc-CSF) have suggested significant clinical utilit y although little is known regarding the effect of these cytokines when adm inistered during pregnancy. rhSCF (25 mu g/kg/day) +/- rhG-CSF (50 mu g/kg/ day) were administered chronically to gravid rhesus monkeys (n = 12) or dir ectly to the rhesus fetus (n = 2) during the second and third trimesters. M aternal/fetal blood samples were collected to assess circulating SCF/G-CSF levels and complete blood counts compared to non-treated animals (n = 40). Fetal endogenous SCF levels were four-fold greater than the dam (fetus simi lar to 2500 pg/ml, dam similar to 500 pg/ml), whereas circulating G-CSF was similar in the fetal/maternal compartments (similar to 50-100 pg/ml). Ther e were no adverse effects detected in the fetus or dam as a result of SCF /- G-CSF administration. Although high levels of SCF and G-CSF were achieve d in the maternal circulation with maternal administration (SCF: 7000-15 00 0 pg/ml; G-CSF: 7000-54 000 pg/ml), there was little evidence of placental transport or effects on fetal haematopoiesis. In contrast, direct fetal adm inistration of SCF + G-CSF resulted in a rapid rise in fetal neutrophil cou nts. These studies have shown the monkey to be an excellent model for study ing haematopoietic interventions during gestation, and suggest the best app roach for achieving haematopoietic changes in the fetus and newborn is by d irect in utero administration. (C) 1999 Academic Press.