title: Vascularized tissue-engineered chambers promote survival and function of transplanted islets and improve glycemic control.
abstract: We have developed a chamber model of islet engraftment that optimizes islet survival by rapidly restoring islet-extracellular matrix relationships and vascularization. Our aim was to assess the ability of syngeneic adult islets seeded into blood vessel-containing chambers to correct streptozotocin-induced diabetes in mice. Approximately 350 syngeneic islets suspended in Matrigel extracellular matrix were inserted into chambers based on either the splenic or groin (epigastric) vascular beds, or, in the standard approach, injected under the renal capsule. Blood glucose was monitored weekly for 7 weeks, and an intraperitoneal glucose tolerance test performed at 6 weeks in the presence of the islet grafts. Relative to untreated diabetic animals, glycemic control significantly improved in all islet transplant groups, strongly correlating with islet counts in the graft (P<0.01), and with best results in the splenic chamber group. Glycemic control deteriorated after chambers were surgically removed at week 8. Immunohistochemistry revealed islets with abundant insulin content in grafts from all groups, but with significantly more islets in splenic chamber grafts than the other treatment groups (P<0.05). It is concluded that hyperglycemia in experimental type 1 diabetes can be effectively treated by islets seeded into a vascularized chamber functioning as a "pancreatic organoid."
authors.affiliation: Bernard O'Brien Institute of Microsurgery and Dept. of Surgery, University of Melbourne, Melbourne, Victoria, Australia. kenneth.knight@svhm.org.au
authors.forename: K R
authors.initials: KR
authors.lastname: Knight
authors.forename: Y
authors.initials: Y
authors.lastname: Uda
authors.forename: M W
authors.initials: MW
authors.lastname: Findlay
authors.forename: D L
authors.initials: DL
authors.lastname: Brown
authors.forename: K J
authors.initials: KJ
authors.lastname: Cronin
authors.forename: E
authors.initials: E
authors.lastname: Jamieson
authors.forename: T
authors.initials: T
authors.lastname: Tai
authors.forename: E
authors.initials: E
authors.lastname: Keramidaris
authors.forename: A J
authors.initials: AJ
authors.lastname: Penington
authors.forename: J
authors.initials: J
authors.lastname: Rophael
authors.forename: L C
authors.initials: LC
authors.lastname: Harrison
authors.forename: W A
authors.initials: WA
authors.lastname: Morrison
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D003094:Collagen; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000601:surgery*; D004338:Drug Combinations; D005951:Glucose Tolerance Test; D006085:Graft Survival; D006119:Groin; D007328:Insulin / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation / Q000295:instrumentation*; D007668:Kidney; D007797:Laminin; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D011509:Proteoglycans; D013154:Spleen; D023822:Tissue Engineering / Q000295:instrumentation*; D016042:Transplantation, Heterotopic / Q000295:instrumentation*; D014184:Transplantation, Homologous
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D007328:Insulin; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen