Fetal Cells from Maternal Blood - A Powerful tool for Prenatal Diagnosis

(Abstract published in the proceedings of ISPD 2010, Amsterdam)

Marie Brinch, Lotte Hatt, Ripudaman Singh, Kristine Møller, Rune Hoff Lauridsen, Helle Kristensen, Maja B. Kristensen, Marianne Mose Hansen, Marianne Rasmussen, Simon Tabi  Arrey, Trine Overgaard Petersen, Steen Kølvraa, Britta Christensen*

FCMB ApS. Tysklandsvej 7. Vejle 7100. Denmark. Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it *

Circulating fetal cells in maternal blood provide a powerful tool for risk-free, non-invasive prenatal diagnosis of fetal anomalies. Since late 19th century, scientists have known that fetal cells do circulate in maternal blood. However, due to lack of knowledge on fetal cell specific markers and suitable methods to enrich these rare cells, the potential of circulating fetal cells for non-invasive prenatal diagnosis has not been fully acknowledged. We at FCMB have developed a novel method to enrich rare fetal cells from maternal blood. The fetal origin of the enriched cells was confirmed by doing XY chromosome-specific FISH on pregnancies bearing a male fetus. We used 100 fetal cells (in a biological replicate of 2) to prepare cDNA for microarray analysis. A comparison of the array data from the fetal cells and the surrounding maternal blood cells revealed unique fetal cell markers which were used for gender-independent isolation/identification of fetal cells from maternal blood. To confirm this we performed a feasibility study where intravenous blood was collected from 100 pregnant women (gestation age 11 to 14 weeks). Fetal cells were isolated from maternal blood by magnetic cell sorting using ‘FCMB cocktail-1’ antibodies. The cells were stained using ‘FCMB cocktail-2’ and later identified by automated scanning. The gender of the fetal cells identified by antibody staining was determined by XY-FISH and matched with gender determined by Y specific PCR on free fetal DNA from maternal plasma. There was a 99% correlation between the results of gender analysis on fetal cells by XY-FISH and gender analysis on free fetal DNA, confirming our ability to enrich and detect fetal cells in a gender-independent manner. Taking lead from our ability to successfully isolate fetal cells, we are now doing a feasibility study on high risk pregnancies.