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
References
Feb 19, 2004·Human Immunology·Yunyuan LiAziz Ghahary
Oct 2, 2004·Nature Reviews. Immunology·Andrew L Mellor, David H Munn
Aug 29, 2006·Diabetes·Nan ZhangH Henry Dong
May 5, 2007·Journal of Cellular Physiology·Reza B JaliliAziz Ghahary
Jun 15, 2007·World Journal of Surgery·Garth L WarnockDavid Thompson
Oct 4, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maria L BelladonnaPaolo Puccetti
Dec 17, 2008·The American Journal of Pathology·Reza B JaliliAziz Ghahary
May 30, 2009·Cell Transplantation·John C StendahlSamuel I Stupp
Jun 19, 2009·Expert Opinion on Therapeutic Targets·P H Tan, A K Bharath
Oct 3, 2009·Cell Transplantation·UNKNOWN CITR Research Group
May 29, 2010·Diabetes·R Paul Robertson
Jun 5, 2010·Diabetes·Reza B JaliliAziz Ghahary
Sep 18, 2010·The Journal of Gene Medicine·Inge PetrusThierry VandenDriessche
Oct 7, 2010·Journal of Diabetes·Shinichi Matsumoto
Jan 5, 2011·Transplantation·Nassir RostambeigiYogish C Kudva
Apr 21, 2011·Journal of Cellular Physiology·Reza B JaliliAziz Ghahary
May 17, 2011·Acta Biomaterialia·R HartwellA Ghahary
Oct 11, 2011·Archivum Immunologiae Et Therapiae Experimentalis·Natasha A DetersJenny E Gunton
Aug 21, 2012·The American Journal of Pathology·Yun ZhangAziz Ghahary
Oct 9, 2012·Clinical and Experimental Immunology·V J AuerM J Stangl
Nov 10, 2012·Diabetes·Éva KorposLydia Sorokin
Sep 28, 2013·Canadian Journal of Diabetes·Azadeh Hosseini-TabatabaeiAziz Ghahary
Citations
Jan 9, 2016·Journal of Cellular Physiology·Yun ZhangAziz Ghahary
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
May 14, 2016·Biomedical Materials·Alexandra M SminkPaul de Vos
Nov 9, 2019·Journal of Tissue Engineering·Gabriel Alexander SalgHannes Götz Kenngott
Jun 18, 2017·Respiratory Research·Guoping ZhengJianguo Xu
Jul 2, 2019·Biomedical Reports·Maria SounidakiIoannis Stefanidis
Jul 18, 2015·Clinical Science·Amanda W S YeungShane R Thomas
Mar 7, 2021·International Journal of Molecular Sciences·Ruta ZulpaitePeter Schemmer