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- Title
Improved Vascular Engraftment and Graft Function After Inhibition of the Angiostatic Factor Thrombospondin-1 in Mouse Pancreatic Islets.
- Authors
Olerud, Johan; Johansson, Magnus; Lawler, Jack; Welsh, Nils; Carlsson, Per-Ola
- Abstract
OBJECTIVE--Insufficient development of a new intra-islet capillary network after transplantation may be one contributing factor to the failure of islet grafts in clinical transplantation. The present study tested the hypothesis that the angiostatic factor thrombospondin-1 (TSP-1), which is normally present in islets, restricts intra-islet vascular expansion posttransplantation. RESEARCH DESIGN AND METHODS--Pancreatic islets of TSP-l--deficient (TSP-1[sup -/-]) mice or wild-type islets transfected with siRNA for TSP-1 were transplanted beneath the renal capsule of syngeneic or immunocompromised recipient mice. RESULTS--Both genetically TSP-1[sup -/-] islets and TSP-1 siRNA-transfected islet cells demonstrated an increased vascular density when compared with control islets 1 month after transplantation. This was also reflected in a markedly increased blood perfusion and oxygenation of the grafts. The functional importance of the improved vascular engraftment was analyzed by comparing glucose-stimulated insulin release from islet cells transfected with either TSP-1 siRNA or scramble siRNA before implantation. These experiments showed that the increased revascularization of grafts composed of TSP-1 siRNA-transfected islet cells correlated to increments in both their first and second phase of glucose-stimulated insulin secretion. CONCLUSIONS--Our findings demonstrate that inhibition of TSP-1 in islets intended for transplantation may be a feasible strategy to improve islet graft revascularization and function. Diabetes 57:1870-1877, 2008
- Subjects
THROMBOSPONDINS; ISLANDS of Langerhans; LABORATORY mice; INSULIN; SMALL interfering RNA
- Publication
Diabetes, 2008, Vol 57, Issue 7, p1870
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db07-0724