Expandability of haemopoietic progenitors in first trimester fetal and maternal blood: implications for non-invasive prenatal diagnosis.
OBJECTIVE
Selective amplification of rare fetal cells in maternal blood is a potential strategy for non-invasive prenatal diagnosis. We assessed the proliferative potential of first trimester fetal progenitors compared to maternal ones.


METHODS
Fetal and maternal haemopoietic progenitors were cultured separately and in two model mixtures: (i) co-cultures of male fetal nucleated cells mixed with maternal nucleated cells and (ii) co-cultures of malefetal CD34+ cells with maternal CD34+ cells. Cell origin was detected by X-Y fluorescence in situ hybridisation (FISH) RESULTS: The frequency of haemopoietic progenitors in first trimester fetal blood (predominantly CFU-GEMM) differed from those in peripheral blood from pregnant women (predominantly BFU-e). First trimester haemopoietic progenitors formed larger colonies (p=0.0001) and their haemoglobinisation was accelerated compared to those of maternal origin (p<0.001). CD34+ fetal haemopoietic progenitor cells could be expanded four times more than their maternal counterparts (median 235.8-fold, range 174.0-968.0 vs 71.9-fold, range 41.1-192.0; p=0.003). While selective expansion of fetal cells was not observed in the mononuclear cell model, the CD34+ cell rare event mixtures produced a 463.2-fold (range 128.0-2915.0) expansion of fetal cells.


CONCLUSIONS
Selective expansion of first trimester fetal haemopoietic progenitors may be useful for amplifying fetal cells from maternal blood.
Department of Maternal and Fetal Medicine, Institute of Reproductive and Developmental Biology, Imperial College of Science, Technology and Medicine, London, UK.
Cesare
C
Campagnoli
Irene A G
IA
Roberts
Sailesh
S
Kumar
Mahesh
M
Choolani
Phillip R
PR
Bennett
Elizabeth
E
Letsky
Nicholas M
NM
Fisk
D018952:Antigens, CD34 / Q000032:analysis; D002452:Cell Count; D002455:Cell Division; D002478:Cells, Cultured; D018920:Coculture Techniques; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000166:cytology; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011296:Prenatal Diagnosis / Q000379:methods*
D018952:Antigens, CD34; D006454:Hemoglobins