In Vitro Hyperglycemia or a Diabetic Intrauterine Environment Reduces Neonatal Endothelial Progenitor Cell Function

Objective: Emerging data demonstrate that maternal diabetes mellitus (DM) has longterm health consequences for her offspring including the development of hypertension. In adults, circulating endothelial progenitor cells (EPCs) participate in vascular repair, and EPC numbers and function inversely correlate with the risk of developing vascular disease. Therefore, our objectives were to determine whether hyperglycemia (HG) or exposure to a diabetic intrauterine environment alters EPC function. Research Design and Methods: We utilized well established clonogenic endothelial colony forming cell (ECFC) assays and murine transplantation experiments to examine human vasculogenesis. Results: Both in vitro HG and a diabetic intrauterine environment reduced ECFC colony formation, self-renewal capacity, and capillary-like tube formation in matrigel. This cellular phenotype was linked to premature senescence and reduced proliferation. Further, cord blood ECFCs from diabetic pregnancies formed fewer chimeric vessels de novo after transplantation into immunodeficient mice compared to neonatal ECFCs harvested from uncomplicated pregnancies. Conclusions: Collectively, these data demonstrate that HG or exposure to a diabetic intrauterine environment diminishes neonatal ECFC function both in vitro and in vivo, providing potential mechanistic insights into the long-term cardiovascular complications observed in newborns of diabetic pregnancies. GRANT SUPPORT. KO8 CA096579 (D.A.I.), R21 HL08885 (D.A.I and L.S.H.), P30 CA82709 (D.A.I. and L.S.H.), and the Riley Children’s Foundation (D.A.I. and L.S.H.)