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-colony stimulating factor (rhG-CSF) have suggested significant clinical utility although little is known regarding the effect of these cytokines when administered during pregnancy. rhSCF (25 microg/kg/day)+/-rhG-CSF (50 microg/kg/day) were administered chronically to gravid rhesus monkeys ( n =12) or directly to the rhesus fetus ( n=2) during the second and third trimesters. Maternal/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 approximately 2500 pg/ml, dam approximately 500 pg/ml), whereas circulating G-CSF was similar in the fetal/maternal compartments ( approximately 50-100 pg/ml). There 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 achieved in the maternal circulation with maternal administration (SCF: 7000-15 000 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 administration of SCF+G-CSF resulted in a rapid rise in fetal neutrophil counts. These studies have shown the monkey to be an excellent model for studying haematopoietic interventions during gestation, and suggest the best approach for achieving haematopoietic changes in the fetus and newborn is by direct in utero administration.