Differential effects of interleukin-3 on fetal and adult erythroid cells in culture: implications for the isolation of fetal cells from maternal blood

Fetal clonogenic erythroid cells may be present in maternal blood and serve as a source of fetal DNA for prenatal genetic diagnosis. Proliferating nuc leated red cells in cultures from first and second trimester fetal blood co ntain only fetal haemoglobin (HbF; F+A- cells), whereas nucleated red cells from adult blood contain also adult haemoglobin (HbA; F+A or F-A+ cells). Thus, fetal red cells can be identified and How sorted. However, a few adul t cells are also F+A-. which reduces the purity of fetal cell isolation. Cu lture media optimized for erythropoiesis contain interleukin-3 (IL3). We sh ow here that IL3 strongly stimulates the growth of F+ cells (both F+A- and F+A+) in cultures from adult blood but has only a comparatively small effec t on F+A- cells in cultures from fetal blood. This difference is maintained in the unified conditions of co-cultures of adult and fetal cells, so that the purity of fetal cell sorts can be increased by omitting IL3 from the c ulture medium. We further show that IL3 accelerates the exhaustion of the l ong-term division potential of adult cells, allowing fetal secondary coloni es to be identified by their size following a two-stage culture scheme. Thu s, the choice to omit or include IL3 in the growth medium of maternal blood cultures should depend on whether fetal nucleated red cells are to be isol ated by flow sorting after one week, or by picking secondary colonies after a later secondary culture stage. Copyright (C) 2000 John Wiley & Sons, Ltd .