Immunoprotection and Functional Improvement of Allogeneic Islets in Diabetic Mice, Using a Stable Indoleamine 2,3-Dioxygenase Producing Scaffold

Transplantation
Azadeh Hosseini-TabatabaeiAziz Ghahary

Abstract

We have previously shown that an immunomodulatory enzyme, indoleamine 2,3-dioxygenase (IDO) in dermal fibroblasts generates a tryptophan-deficient environment that selectively inhibits proliferation and induces apoptosis of bystander CD4+ and CD8+ T cells, but not pancreatic islets. Because these immune cells are involved in islet allograft rejection, we hypothesized that transplantation of islets embedded in a novel 3-dimensional composite scaffold within which stable IDO-expressing fibroblasts serve as source of local immunosuppression would lead to normoglycemia in a streptozotocin-induced diabetic mouse model. Islet grafts were prepared by embedding stable IDO-expressing fibroblasts and allogeneic islets into a protease-resistant composite scaffold. Islets function and survival were evaluated in vitro using immunohistochemistry. Allografts were transplanted under the kidney capsule of streptozotocin-induced diabetic mice; viability, function, and criteria for graft take were evaluated. Flow cytometry was performed to determine specific intragraft, draining lymph nodes and spleen T-cell population, and splenocytes alloantigen responsiveness of graft recipients. The results of a series of in vitro experiments revealed that ID...Continue Reading

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Sep 28, 2013·Canadian Journal of Diabetes·Azadeh Hosseini-TabatabaeiAziz Ghahary

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Citations

May 20, 2016·Experimental Dermatology·Reinhart Speeckaert, Nanja van Geel
Jun 13, 2018·American Journal of Physiology. Endocrinology and Metabolism·Clarissa Hernandez StephensSherry L Voytik-Harbin
Jul 18, 2015·Clinical Science·Amanda W S YeungShane R Thomas
Mar 7, 2021·International Journal of Molecular Sciences·Ruta ZulpaitePeter Schemmer

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