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Vascularized tissue‐engineered chambers promote survival and function of transplanted islets and improve glycemic control
Author(s) -
Knight Kenneth R.,
Uda Yoshiaki,
Findlay Michael W.,
Brown David L.,
Cronin Kevin J.,
Jamieson Emma,
Tai Timothy,
Keramidaris Effie,
Penington Anthony J.,
Rophael John,
Harrison Leonard C.,
Morrison Wayne A.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4879fje
Subject(s) - islet , renal capsule , medicine , diabetes mellitus , streptozotocin , glycemic , insulin , matrigel , transplantation , endocrinology , angiogenesis
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.”