Endothelial colony-Forming cells derived from pregnancies complicated by intrauterine growth restriction are fewer and have reduced vasculogenic capacity

Abstract

Context: Endothelial colony-forming cells (ECFCs) are the only putative endothelial progenitor cells capable of vasculogenesis, and their dysfunction may represent a risk factor for cardiovascular disease. Intrauterine growth restriction (IUGR) is a pregnancy-related disorder associated with long-term cardiovascular risk. Objective: Our objective was to determine whether ECFCs derived from pregnancies complicated by IUGR exhibit altered vasculogenic potential. Design and Setting: This was a prospective cohort study; patients were recruited at St. Mary's Hospital, Manchester, United Kingdom. Participants: Twenty-three women with normal pregnancies and 13 women with IUGR-complicated pregnancies at gestational ages above 37 weeks were included. Main Outcome Measures: Vasculogenic capacity of rigorously characterized ECFCs was investigated in vivo by measuring blood vessel formation in collagen/fibronectin gels implanted in mice; proliferative, migratory, and chemotactic abilities were assessed in cell culture. Placental uptake of fetal ECFCs, assessed by differences in arterial and venous cord blood content, was determined by flow cytometry. Results: In vivo, IUGR ECFCs formed fewer blood vessels (P < .001) and capillaries (P = .001) compared with normal pregnancy-derived ECFCs. In culture conditions, IUGR ECFCs had reduced proliferation (P = .01) and migration (P = .007) and diminished chemotactic abilities to stromal cell-derived factor 1 (P=.007) coupled with reduced hypoxia-induced matrix metalloproteinase-2 release (P=.02). Finally, in IUGR pregnancies, the number of ECFCs was lower in arterial cord blood (P = .002) and placental uptake of cells was reduced (P < .001). Conclusions: ECFCs derived from IUGR cord blood are rarefied and dysfunctional, resulting in diminished vasculogenic potential; this could be a cause of placental dysfunction in IUGR, with long-term postnatal implications for cardiovascular function in ffspring. © 2013 by The Endocrine Society.