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Characterization of Fetal Cells from the Maternal Circulation by Microarray Gene Expression Analysis – Could the Extravillous Trophoblasts Be a Target for Future Cell-Based Non-Invasive Prenatal Diagnosis?

Introduction: Circulating fetal cells in maternal blood pro- vide a tool for risk-free, non-invasive prenatal diagnosis. However, fetal cells in the maternal circulation are scarce, and to effectively isolate enough of them for reliable diag- nostics, it is crucial to know which fetal cell type(s) should be targeted. Materials and Methods: Fetal cells were enriched from maternal blood by magnetic-activated cell sorting us- ing the endothelial cell marker CD105 and identified by XY fluorescence in situ hybridization. Expression pattern was compared between fetal cells and maternal blood cells using stem cell microarray analysis. Results: 39 genes were identi- fied as candidates for unique fetal cell markers. More than half of these are genes known to be expressed in the pla- centa, especially in extravillous trophoblasts (EVTs). Immu-

nohistochemical staining of placental tissue confirmed CD105 staining in EVTs and 76% of fetal cells enriched by CD105 were found to be cytokeratin-positive. Discussion: The unique combination of mesodermal (CD105) and ecto- dermal (cytokeratin) markers in EVTs could be a potential marker set for cell enrichment of this cell type in maternal blood and could be the basis for future cell-based non-invasive prenatal diagnosis.