4.7 Article

Donor Islet Endothelial Cells in Pancreatic Islet Revascularization

Journal

DIABETES
Volume 60, Issue 10, Pages 2571-2577

Publisher

AMER DIABETES ASSOC
DOI: 10.2337/db10-1711

Keywords

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Funding

  1. Juvenile Diabetes Research Foundation (JDRF) [5-2005-1277]
  2. Diabetes Research Institute Foundation (DRIF)
  3. Lars-Erik Gelin Memorial Foundation
  4. Swedish Research Council
  5. Novo Nordisk Foundation
  6. European Foundation for the Study of Diabetes
  7. Karolinska Institutet
  8. Swedish Diabetes Association
  9. Berth von Kantzow's Foundation
  10. World Class University through the National Research Foundation of Korea
  11. Ministry of Education, Science, and Technology [R31-2008-000-10105-0]
  12. Torsten and Ragnar Soderberg Foundation
  13. Skandia Insurance Company, Ltd.
  14. Knut and Alice Wallenberg Foundation
  15. VIBRANT [FP7-228933-2]
  16. Family Erling-Persson Foundation
  17. Wenner-Gren Foundation
  18. National Institutes of Health [5U19-AI-050864-10]
  19. Novo Nordisk Fonden [NNF11OC1014706] Funding Source: researchfish

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OBJECTIVE-Freshly isolated pancreatic islets contain, in contrast to cultured islets, intraislet endothelial cells (ECs), which can contribute to the formation of functional blood vessels after transplantation. We have characterized how donor islet endothelial cells (DIECs) may contribute to the revascularization rate, vascular density, and endocrine graft function after transplantation of freshly isolated and cultured islets. RESEARCH DESIGN AND METHODS-Freshly isolated and cultured islets were transplanted under the kidney capsule and into the anterior chamber of the eye. Intravital laser scanning microscopy was used to monitor the revascularization process and DIECs in intact grafts. The grafts' metabolic function was examined by reversal of diabetes, and the ultrastructural morphology by transmission electron microscopy. RESULTS-DIECs significantly contributed to the vasculature of fresh islet grafts, assessed up to 5 months after transplantation, but were hardly detected in cultured islet grafts. Early participation of DIECs in the revascularization process correlated with a higher revascularization rate of freshly isolated islets compared with cultured islets. However, after complete revascularization, the vascular density was similar in the two groups, and host ECs gained morphological features resembling the endogenous islet vasculature. Surprisingly, grafts originating from cultured islets reversed diabetes more rapidly than those originating from fresh islets. CONCLUSIONS-In summary, DIECs contributed to the revascularization of fresh, but not cultured, islets by participating in early processes of vessel formation and persisting in the vasculature over long periods of time. However, the DIECs did not increase the vascular density or improve the endocrine function of the grafts. Diabetes 60:2571-2577, 2011

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