HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: db07-0724v1 57/7/1870    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Olerud, J. Articles by Carlsson, P.-O. Search for Related Content PubMed PubMed Citation Articles by Olerud, J. Articles by Carlsson, P.-O. Social Bookmarking                What's this?

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

¹ Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
² Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
³ Department of Medical Sciences, Uppsala University, Uppsala, Sweden

Corresponding author: Per-Ola Carlsson, per-ola.carlsson{at}mcb.uu.se

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.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Brissova and A. C. Powers Revascularization of Transplanted Islets: Can It Be Improved? Diabetes, September 1, 2008; 57(9): 2269 - 2271. [Full Text] [PDF]