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-1-deficient (TSP-1(-/-)) 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(-/-) 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.
journal_name
Diabetesjournal_title
Diabetesauthors
Olerud J,Johansson M,Lawler J,Welsh N,Carlsson POdoi
10.2337/db07-0724subject
Has Abstractpub_date
2008-07-01 00:00:00pages
1870-7issue
7eissn
0012-1797issn
1939-327Xpii
db07-0724journal_volume
57pub_type
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