help button home button Am J Pathol Epitomics, Inc.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Originally published online as doi:10.2353/ajpath.2009.080539 on December 12, 2008

Published online before print December 12, 2008
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
ajpath.2009.080539v1
174/1/196    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jalili, R. B.
Right arrow Articles by Ghahary, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jalili, R. B.
Right arrow Articles by Ghahary, A.
(American Journal of Pathology. 2009;174:196-205.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080539

Mouse Pancreatic Islets Are Resistant to Indoleamine 2,3 Dioxygenase-Induced General Control Nonderepressible-2 Kinase Stress Pathway and Maintain Normal Viability and Function

Reza B. Jalili*{dagger}, Farshad Forouzandeh*, Alireza Moeenrezakhanlou*, Gina R. Rayat{ddagger}, Ray V. Rajotte{ddagger}, Hasan Uludag§ and Aziz Ghahary*

From the Department of Surgery,* University of British Columbia, Vancouver, British Columbia, Canada; the Endocrinology and Metabolism Research Center,{dagger} Medical Sciences/University of Tehran, Tehran, Iran; the Surgical-Medical Research Institute,{ddagger} Department of Chemical and Materials Engineering,§ and the Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada

Islet transplantation is a promising treatment for diabetes. However, it faces several challenges including requirement of systemic immunosuppression. Indoleamine 2,3-dioxygenase (IDO), a tryptophan degrading enzyme, is a potent immunomodulatory factor. Local expression of IDO in bystander fibroblasts suppresses islet allogeneic immune response in vitro. The aim of the present study was to investigate the impact of IDO on viability and function of mouse islets embedded within IDO-expressing fibroblast-populated collagen scaffold. Mouse islets were embedded within collagen matrix populated with IDO adenovector-transduced or control fibroblasts. Proliferation, insulin content, glucose responsiveness, and activation of general control nonderepressible-2 kinase stress-responsive pathway were then measured in IDO-exposed islets. In vivo viabilities of composite islet grafts were also tested in a syngeneic diabetic animal model. No reduction in islet cells proliferation was detected in both IDO-expressing and control composites compared to the baseline rates. Islet functional studies showed normal insulin content and secretion in both preparations. In contrast to lymphocytes, general control nonderepressible-2 kinase pathway was not activated in islets cocultured with IDO-expressing fibroblasts. When transplanted to diabetic mice, syngeneic IDO-expressing composite islet grafts were functional up to 100 days tested. These findings collectively confirm normal viability and functionality of islets cocultured with IDO-expressing cells and indicate the feasibility of development of a functional nonrejectable islet graft.




This article has been cited by other articles:


Home page
 JEMHome page
F. Fallarino, G. Luca, M. Calvitti, F. Mancuso, C. Nastruzzi, M. C. Fioretti, U. Grohmann, E. Becchetti, A. Burgevin, R. Kratzer, et al.
Therapy of experimental type 1 diabetes by isolated Sertoli cell xenografts alone
J. Exp. Med., October 26, 2009; 206(11): 2511 - 2526.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2009 by the American Society for Investigative Pathology.