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

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 if 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 inhibitor and overexpression studies. Results GDM ECFCs were more proliferative than control ECFCs. However, GDM ECFCs exhibited decreased network forming ability in Matrigel. Aging of ECFCs by serial passaging led to increased senescence and reduced proliferation of GDM ECFCs. ECFCs from GDM pregnancies were resistant to hyperglycemia-induced senescence compared to controls. In response to hyperglycemia, control ECFCs activated p38MAPK, which was required for hyperglycemia-induced senescence. In contrast, GDM ECFCs had no change in p38MAPK activation under equivalent conditions. Conclusion Intrauterine exposure of ECFCs to GDM induces unique phenotypic alterations. The resistance of GDM ECFCs to hyperglycemia-induced senescence and decreased p38MAPK suggest that these progenitor cells have undergone changes to induce tolerance to a hyperglycemic environment.

Transgelin induces dysfunction of fetal endothelial colony-forming cells from gestational diabetic pregnancies

“…As a result of intrauterine GDM exposure, ECFCs exhibit vasculogenic dysfunction (3,21). Reduction of TAGLN in ECFCs from uncomplicated pregnancies were transduced with TAGLN-containing lentivirus (TAGLN OE).…”

“…ECFC cell culture. ECFCs were isolated from umbilical cord blood samples by the Indiana University Simon Cancer Center Angio BioCore as previously described (3). Eight independent preparations were used for both uncomplicated and gestational diabetes mellitusexposed samples (UC: n ϭ 8; GDM: n ϭ 8).…”

“…Fetal ECFCs display significant functional impairments as a result of exposure to maternal diabetes in utero (3,21). However, the molecular mechanisms underlying the observed phenotypic differences in number and function are largely unknown.…”

Tissue regeneration using endothelial colony-forming cells: promising cells for vascular repair

“…For older children and adult subjects, primary circulating ECFCs from peripheral blood (PB-ECFC) are less clonogenic, proliferative, and angiogenic than CB-ECFCs. Finally, it is well known that certain disease states, such as diabetes, can significantly diminish the frequency and function of the isolated ECFC to such an extent that these cells would not be of sufficient quality for use as a revascularization therapy (77,78).…”

Endothelial Progenitor Cells as Prognostic Markers of Preterm Birth-Associated Complications

“…These properties are crucial during organogenesis and postnatal development . Mounting evidence suggests EPCs are altered by disorders of pregnancy that can be associated with preterm birth such as diabetes and pre‐eclampsia , . Furthermore, lower numbers of endothelial colony‐forming cells (ECFCs), a subset of EPCs capable of self‐renewal and de novo vessel formation, were also associated with the development of bronchopulmonary dysplasia (BPD) , .…”