Umbilical Cord Blood Circulating Progenitor Cells and Endothelial Colony-Forming Cells Are Decreased in Preeclampsia

Abstract

Preeclampsia (PE) is a pregnancy-specific disease characterized by the new onset of hypertension and proteinuria. Mothers with PE are known to develop endothelial dysfunction, but its effect on infants has been understudied, as newborns are often asymptomatic. Recent studies indicate that infants born from preeclamptic pregnancies develop endothelial dysfunction including higher blood pressure during childhood and an increased risk of stroke later in life. We hypothesize that PE reduces the number and function of fetal angiogenic progenitor cells and may contribute to this increased risk. We quantified 2 distinct types of angiogenic progenitors, pro-angiogenic circulating progenitor cells (CPCs) and endothelial colony-forming cells (ECFCs), from the umbilical cord blood of preeclamptic pregnancies and normotensive controls. Pro-angiogenic and nonangiogenic CPCs were enumerated via flow cytometry and ECFCs by cell culture. Additionally, we studied the growth, migration, and tube formation of ECFCs from PE and gestational age-matched normotensive control pregnancies. We found that PE resulted in decreased cord blood pro-angiogenic CPCs and ECFCs. Nonangiogenic CPCs were also decreased. Preeclamptic ECFCs demonstrated decreased growth and migration but formed tube-like structures in vitro similar to controls. Our results suggest that the preeclamptic environment alters the number and function of angiogenic progenitor cells and may increase the risk of later vascular disease.

Examining the role of unmeasured confounding in mediation analysis with genetic and genomic applications

“…A relevant clinical example is the pathway by which maternal preeclampsia contributes to the risk of chronic lung disease in the newborn [ 5 ]. The effects of preeclampsia (exposure A) on the developing lung (outcome Y) are mediated by disruptions in angiogenesis (mediator M), indicated by altered pro-angiogenic umbilical cord blood biomarkers [ 4 , 13 ]. However, preterm birth (measured confounder C) may confound the mediator-outcome relationship, as the degree of prematurity is associated with both severe lung disease [ 9 ] and levels of pro-angiogenic biomarkers [ 1 ].…”

Recent advances in antenatal factors predisposing to bronchopulmonary dysplasia

“…49 Decreased numbers of endothelial progenitor cells have been demonstrated in the cord blood of preterm newborns who develop BPD, 50,51 cells which are also decreased in maternal diabetes and pre-eclampsia. 52,53 Interestingly, cord blood from pregnancies with a placenta that demonstrated severe maternal vascular under-perfusion had lower levels of placental grow factor (PIGF), granulocyte-colony stimulating factor (G-CSF) and VEGF-A. 34 This pattern was consistent in cord blood of those infants who were later diagnosed with BPD complicated by echocardiographic findings of PH, but only the relationship with PIGF and G-CSF held up in a validation cohort.…”

Endothelial Progenitor Cells of the Human Placenta and Fetoplacental Circulation: A Potential Link to Fetal, Neonatal, and Long-term Health

“… Circulating progenitor cell (CPC) flow cytometry gating strategy adapted from Gumina et al ( 23 ) . Here, peripheral blood mononuclear cells were analyzed by polychromatic flow cytometry.…”

“…With regard to preeclampsia, different groups of investigators have demonstrated both reductions in circulating number and abnormal function of ECFCs isolated from the venous cord blood of babies born to preeclamptic mothers ( 23 , 32 , 33 ). Specifically, Gumina et al showed a decrease in both pro- and non-angiogenic subsets of CPCs identifiable by flow cytometry in pregnancies complicated by preeclampsia in comparison to normotensive controls.…”

“…All three reports also indicate fewer ECFC colony numbers in their respective preeclamptic populations. From a functional perspective, two groups reported that ECFCs from cord blood of preeclamptic pregnancies demonstrated diminished growth and migration ( 23 , 32 ), while other laboratories found no difference in ECFC tube formation ( 23 , 33 ). However, von Versen-Höynck et al demonstrated a deficiency in preeclamptic ECFC tube formation, with partial improvement with vitamin D3 treatment ( 32 ).…”