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Fetal Endothelial Colony Forming Cells from pregnancies complicated by intrauterine growth restriction have reduced vasculogenic capacity
Author(s) -
Bourque Stephane Louis,
Sipos Peter,
Sibley Colin,
Baker Philip,
Davidge Sandra,
Crocker Ian
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.683.1
Subject(s) - cord blood , andrology , intrauterine growth restriction , fetus , hypoxia (environmental) , medicine , umbilical cord , flow cytometry , cd34 , pregnancy , immunology , stem cell , biology , chemistry , genetics , organic chemistry , oxygen
Background Diminished numbers of ECFCs may be a risk factor for cardiovascular disease (CVD). Intrauterine growth restriction (IUGR) is a pregnancy complication associated with neonatal morbidity and mortality and long‐term sequelae, including CVD. We hypothesized that fetal ECFCs from human IUGR pregnancies would be fewer in number and exhibit altered vasculogenic potential. Methods Cord blood from uncomplicated and IUGR pregnancies were collected at delivery. ECFCs were counted by flow cytometry using discriminators: 7AAD‐/CD31bright/CD45‐/KDR+/CD34+. Vasculogenic potential was investigated by implanting collagen matrices populated with ECFCs into adult immuno‐deficient mice. Results ECFC numbers were 67% lower in IUGR cord blood vs. controls (P<0.001), and exhibited a 71% longer doubling time (P=0.01). Blood vessel formation was reduced in collagen implants populated with IUGR‐derived ECFCs. In vitro, hypoxia (1% O 2 , 72h) induced‐ECFC senescence, and IUGR cells were more susceptible (P<0.05). Finally, IUGR‐derived ECFCs showed a 61% reduction in MMP‐2 release under hypoxic conditions (P<0.001). Conclusion ECFCs from IUGR cord blood have intrinsic functional alterations, resulting in diminished vasculogenic potential and increased susceptibility to hypoxia. Supported by grants from the Canadian Institutes of Health Research and the Wellcome Trust.