Improved Vascular Engraftment and Graft Function After Inhibition of the Angiostatic Factor Thrombospondin-1 in Mouse Pancreatic Islets

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Improved Vascular Engraftment and Graft Function After Inhibition of the Angiostatic Factor Thrombospondin-1 in Mouse Pancreatic Islets

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Title: Improved Vascular Engraftment and Graft Function After Inhibition of the Angiostatic Factor Thrombospondin-1 in Mouse Pancreatic Islets
Author: Olerud, Johan; Johansson, Magnus; Welsh, Nils; Carlsson, Per-Ola; Lawler, Jack William

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Citation: Olerud, Johan, Magnus Johansson, Jack Lawler, Nils Welsh, and Per-Ola Carlsson. 2008. Improved vascular engraftment and graft function after inhibition of the angiostatic factor thrombospondin-1 in mouse pancreatic islets. Diabetes 57(7): 1870-1877.
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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.
Published Version: doi://10.2337/db07-0724
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453615/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:8097016
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