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Published online December 17, 2007
Diabetes 57:724-731, 2008
DOI: 10.2337/db07-1507
© 2008 by the American Diabetes Association
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In Vitro Hyperglycemia or a Diabetic Intrauterine Environment Reduces Neonatal Endothelial Colony-Forming Cell Numbers and Function

David A. Ingram1,2, Izlin Z. Lien1, Laura E. Mead1, Myka Estes1, Daniel N. Prater1, Ethel Derr-Yellin1, Linda A. DiMeglio1, and Laura S. Haneline1,3

1 Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana
2 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana
3 Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana

Address correspondence and reprint requests to Laura S. Haneline, Herman B. Wells Center for Pediatric Research, 1044 W. Walnut St., R4-476, Indianapolis, IN 46202. E-mail: lhanelin{at}iupui.edu

Key Words: ECFC, endothelial colony-forming cell • EPC, endothelial progenitor cell • MNC, mononuclear cell • SA-β-gal, senescence-associated β-galactosidase

OBJECTIVE—Emerging data demonstrate that maternal diabetes has long-term health consequences for 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 or exposure to a diabetic intrauterine environment alters EPC function.

RESEARCH DESIGN AND METHODS—We used well-established clonogenic endothelial colony-forming cell (ECFC) assays and murine transplantation experiments to examine human vasculogenesis.

RESULTS—Both in vitro hyperglycemia 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 with neonatal ECFCs harvested from uncomplicated pregnancies.

CONCLUSIONS—Collectively, these data demonstrate that hyperglycemia 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.


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