Gestational diabetes induces alterations in the function of neonatal endothelial colony-forming cells

• Published in: Pediatric research Vol. 75; no. 2; pp. 266 - 272
• Main Authors: Blue, Emily K., DiGiuseppe, Robert, Derr-Yellin, Ethel, Acosta, Juan Carlos, Pay, S. Louise, Hanenberg, Helmut, Schellinger, Megan M., Quinney, Sara K., Mund, Julie A., Case, Jamie, Haneline, Laura S.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2014
• Subjects: 692/420; 692/699/2743/137/1926; 692/700/1720; Adult; basic-science-investigation; Cell Proliferation; Cellular Senescence; Collagen - chemistry; Diabetes, Gestational - blood; Drug Combinations; Endothelial Cells - cytology; Enzyme Activation; Female; Fetal Blood - cytology; Humans; Hyperglycemia - metabolism; Hyperglycemia - physiopathology; Infant, Newborn; Laminin - chemistry; Male; Maternal-Fetal Exchange; Medicine & Public Health; p38 Mitogen-Activated Protein Kinases - metabolism; Pediatric Surgery; Pediatrics; Pregnancy; Proteoglycans - chemistry
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1038/pr.2013.224

Background: Children born to mothers with gestational diabetes mellitus (GDM) experience increased risk of developing hypertension, type 2 diabetes mellitus, and obesity. Disrupted function of endothelial colony-forming cells (ECFCs) may contribute to this enhanced risk. The goal of this study was to determine whether cord blood ECFCs from GDM pregnancies exhibit altered functionality. Methods: ECFCs isolated from the cord blood of control and GDM pregnancies were assessed for proliferation, senescence, and Matrigel network formation. The requirement for p38MAPK in hyperglycemia-induced senescence was determined using inhibition and overexpression studies. Results: GDM-exposed ECFCs were more proliferative than control ECFCs. However, GDM-exposed ECFCs exhibited decreased network-forming ability in Matrigel. Aging of ECFCs by serial passaging led to increased senescence and reduced proliferation of GDM-exposed ECFCs. ECFCs from GDM pregnancies were resistant to hyperglycemia-induced senescence compared with those from controls. In response to hyperglycemia, control ECFCs activated p38MAPK, which was required for hyperglycemia-induced senescence. In contrast, GDM-exposed ECFCs showed no change in p38MAPK activation under equivalent conditions. Conclusion: Intrauterine exposure of ECFCs to GDM induces unique phenotypic alterations. The resistance of GDM-exposed ECFCs to hyperglycemia-induced senescence and decreased p38MAPK activation suggest that these progenitor cells have undergone changes that induce tolerance to a hyperglycemic environment.