How useful is the in vitro expansion of fetal CD34+progenitor cells from maternal blood samples for diagnostic purposes?

Fetal cells present in the maternal circulation are a potential source of f etal DNA that can be used for the development of a prenatal diagnostic test . Since their numbers are very low, amplification of fetal cells has been d iscussed for a long time. So far, most studies have focused on culturing fe tal erythroid cells. In this study, we evaluated whether limiting numbers o f fetal haemopoietic progenitor cells present in an excess of maternal cell s were able to overgrow the maternal component. Therefore, we used a model system in which limiting numbers of male CD34+ umbilical cord blood cells w ere diluted in 400 000 female CD34+ peripheral blood cells. The number of X Y positive cells derived from umbilical cord blood was determined using two -colour in situ hybridization with X and Y chromosomal probes. We demonstra ted a 1500-fold relative expansion of male umbilical cord blood cells over the peripheral blood component after three weeks of liquid culture, which a lso corresponded to the extent of expansion of CD34+ cells derived from 20- week fetal blood. However, application of the same culture protocol to mate rnal blood samples obtained at 7-16 weeks of gestation showed no preferenti al growth of fetal haemopoietic progenitor cells. This study, therefore, su ggests that fetal primitive haemopoietic progenitor cells do either not cir culate in maternal blood before 16 weeks of gestation, or require different combinations/concentrations of cytokines for their in vitro expansion. Cop yright (C) 2000 John Wiley & Sons, Ltd.