| First Author | Olerud J | Year | 2008 |
| Journal | Diabetes | Volume | 57 |
| Issue | 7 | Pages | 1870-7 |
| PubMed ID | 18420490 | Mgi Jnum | J:138228 |
| Mgi Id | MGI:3804585 | Doi | 10.2337/db07-0724 |
| Citation | Olerud J, et al. (2008) Improved vascular engraftment and graft function after inhibition of the angiostatic factor thrombospondin-1 in mouse pancreatic islets. Diabetes 57(7):1870-7 |
| abstractText | 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. |
