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

Emily K. Blue, Robert Digiuseppe, Ethel Derr-Yellin, Juan Carlos Acosta, S. Louise Pay, Helmut Hanenberg, Megan M. Schellinger, Sara K. Quinney, Julie A. Mund, Jamie Case, Laura S. Haneline

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)266-272
Number of pages7
JournalPediatric Research
Volume75
Issue number2
DOIs
StatePublished - Feb 2014

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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    Blue, E. K., Digiuseppe, R., Derr-Yellin, E., Acosta, J. C., Pay, S. L., Hanenberg, H., Schellinger, M. M., Quinney, S. K., Mund, J. A., Case, J., & Haneline, L. S. (2014). Gestational diabetes induces alterations in the function of neonatal endothelial colony-forming cells. Pediatric Research, 75(2), 266-272. https://doi.org/10.1038/pr.2013.224