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?
BACKGROUND
Circulating fetal cells in maternal blood provide 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 diagnostics, it is crucial to know which fetal cell type(s) should be targeted.


METHODS
Fetal cells were enriched from maternal blood by magnetic-activated cell sorting using 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 identified as candidates for unique fetal cell markers. More than half of these are genes known to be expressed in the placenta, especially in extravillous trophoblasts (EVTs). Immunohistochemical staining of placental tissue confirmed CD105 staining in EVTs and 76% of fetal cells enriched by CD105 were found to be cytokeratin-positive.


CONCLUSIONS
The unique combination of mesodermal (CD105) and ectodermal (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.
Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark.
Lotte
L
Hatt
Marie
M
Brinch
Ripudaman
R
Singh
Kristine
K
Møller
Rune Hoff
RH
Lauridsen
Niels
N
Uldbjerg
Berthold
B
Huppertz
Britta
B
Christensen
Steen
S
Kølvraa
D002824:Chorionic Villi / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D062145:Maternal Serum Screening Tests / Q000379:methods*; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods; D046888:Tissue Array Analysis / Q000379:methods*; D014327:Trophoblasts / Q000502:physiology*