P030
An endothelial-mesenchymal transition occurs in primary
placental endothelial cells in vitro – could this contribute to
fetal growth restriction?
Stefanie Swietlik, Melissa Westwood,
Edward Johnstone and John Aplin
University of Manchester, Manchester, UK
Fetal growth restriction (FGR) increases risk of perinatal morbidity
and mortality, as well as predisposing to chronic disease in
adult life. Reduced placental vascularisation contributes to FGR.
In other systems, loss of endothelial cells can occur via an
endothelial-mesenchymal transition (EndMT). We hypothesise
that EndMT contributes to hypovascularity in the FGR placenta.
Primary mesenchymal cells outgrowing from first trimester
placental tissue (n=15; 6-15w) were mainly alpha-smooth muscle
actin (αSMA)+. 12% were CD31+, but this decreased to 1%
(p<0.05) by passage 4 with no loss of cell viability. Endothelial
cells were isolated at each passage (iCD31+); 5% expressed
αSMA at isolation, increasing to 35% after 24h. The presence of
internalised anti-CD31 magnetic beads in αSMA+ cells showed
that they had been CD31+ at isolation. The TGFβR-blocker
SB431542 (10µM) reduced acquisition of αSMA in iCD31+ cells.
Dual αSMA+/vWF+ cells were present in the iCD31+ fraction, and
this was also observed in tissue. Experiments using cells from full
term placenta suggested that more iCD31+ cells from FGR tissue
than from normal tissue become αSMA-positive.
Loss of the endothelial marker from the mixed cell population
and gain of the mesenchymal marker in isolated endothelial
cells show an EndMT is occurring in vitro. The presence in
tissue of cells expressing both endothelial and mesenchymal
markers suggests a transitional phenotype. A greater potential for
endothelial cells to undergo EndMT could contribute to FGR.