Vascularized tissue-engineered chambers promote survival and function of transplanted islets and improve glycemic control (Retracted Article. See vol 22, pg 3747, 2008)

Knight, KR; Uda, Y; Findlay, MW; Brown, DL; Cronin, KJ; Jamieson, E; Tai, T; Keramidaris, E; Penington, AJ; Rophael, J; Harrison, LC; Morrison, WA

Author(s): Knight, KR; Uda, Y; Findlay, MW; Brown, DL; Cronin, KJ; Jamieson, E; Tai, T; Keramidaris, E; Penington, AJ; Rophael, J; Harrison, LC; Morrison, WA;
Details: Publication Year 2006-01,Volume 20,Issue #1,Page 565-+
Journal Title: FASEB JOURNAL
Publication Type: Journal Article
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 (R) 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".
Publisher: FEDERATION AMER SOC EXP BIOL
Keywords: TYPE-1 DIABETES-MELLITUS; EXTRACELLULAR-MATRIX; GRAFT-SURVIVAL; MOUSE; ALGINATE; GROWTH; MODEL; MICROENCAPSULATION; GENERATION; MEMBRANE
Publisher's Version: https://doi.org/10.1096/fj.05-4879fje
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2006-01-01 12:00:00