Circulating hematopoietic stem cell populations in human fetuses: implications for fetal gene therapy and alterations with in utero red cell transfusion.

Circulating progenitor cell populations in normal human fetuses and fetuses with various hematological problems were evaluated. Thirty blood samples from 21 human fetuses (17-36 weeks of gestation) were assayed for erythroid, myeloid, and mixed-cell progenitor cells. The mean number of progenitor cells/10(4) blood mononuclear cells in the normal fetal population was 103 +/- 47. Granulomonocytic and mixed progenitor cells (capable of giving rise to both erythroid and myeloid progeny) were the predominant progenitor types in these samples, with pure erythroid progenitors barely detectable. The frequency of progenitor cells in the samples from fetuses with hematological disorders was within the range of normal in all but 1 fetus infected with parvovirus in whom very few progenitor cells were detected. The frequency of progenitor cells in the blood did not change after intravascular red cell transfusion for alloimmunization despite the large volumes transfused, indicating that transfusion may have triggered a release of progenitor cells into the circulation. Progenitor cells in human fetal blood are present in distributions similar to those commonly detected in cord blood. Their total number in the circulating blood is in the same order used for pediatric and adult bone marrow transplantation. These results can be used to calculate the number of colony-forming cells which could be obtained from a fetus by in utero apheresis and which could be made available for autologous fetal gene therapy.