title: Permanent protection of PLG scaffold transplanted allogeneic islet grafts in diabetic mice treated with ECDI-fixed donor splenocyte infusions.
abstract: Allogeneic islet cell transplantation is a promising treatment for human type 1 diabetes. Currently, human islets are transplanted via intra-portal infusions. While successful, it leads to significant early islet attrition from instant blood-mediated inflammatory reaction. An extra-hepatic site was established by transplanting islet-loaded microporous poly(lactide-co-glycolide) (PLG) scaffolds into the epididymal fat pad in syngeneic islet transplant models. This study examined this technology in allogeneic islet transplantation and determined whether transplant tolerance could be effectively induced to protect PLG scaffold transplanted allogeneic islets. The efficacy of an established tolerance induction strategy using donor splenocytes treated with ethylcarbodiimide(ECDI) was tested. ECDI-fixed donor splenocytes were infused 7 days before and 1 day after islet transplantation. Immediate normoglycemia was restored, and treated mice maintained indefinite normoglycemia whereas untreated mice rejected islet grafts within 20 days of transplantation. Interestingly, efficacy of tolerance induction was superior in PLG scaffold compared with intra-portal transplanted islets. Protection of PLG scaffold islet allografts was associated with several mechanisms of immune regulation. In summary, PLG scaffolds can serve as an alternative delivery system for islet transplantation that does not impair tolerance induction. This approach of combining tolerance induction with scaffold islet transplantation has potential therapeutic implications for human islet transplantation.
authors: Division of Nephrology and Hypertension, Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, United States.
authors: Taba
authors: T
authors: Kheradmand
authors: Shusen
authors: S
authors: Wang
authors: Romie F
authors: RF
authors: Gibly
authors: Xiaomin
authors: X
authors: Zhang
authors: Samantha
authors: S
authors: Holland
authors: James
authors: J
authors: Tasch
authors: Jack G
authors: JG
authors: Graham
authors: Dixon B
authors: DB
authors: Kaufman
authors: Stephen D
authors: SD
authors: Miller
authors: Lonnie D
authors: LD
authors: Shea
authors: Xunrong
authors: X
authors: Luo
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002234:Carbodiimides / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D006801:Humans; D007108:Immune Tolerance; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000379:methods*; D008297:Male; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011098:Polyglactin 910 / Q000737:chemistry*; D013154:Spleen / Q000166:cytology*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014184:Transplantation, Homologous
chemical_list: D001672:Biocompatible Materials; D002234:Carbodiimides; D011098:Polyglactin 910