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."

Hyaluronan Benzyl Ester as a Scaffold for Tissue Engineering

“…The adipose tissue was found around mature vessels in addition to newly formed small vascular structures. In summary, these findings demonstrated that hyaluronic acid gel is applicable for generating adipose tissue in gels, displaying adipogenic as well as angiogenic properties, and strongly indicate its use as a matrix material for use as an injectable strategy for soft tissue reconstruction [34]. …”

Neovascularization in an arterio‐venous loop‐containing tissue engineering chamber: role of NADPH oxidase

“…Using this novel in vivo TE chamber, vascularized soft tissues including fat, muscle and connective tissues have been created [2][3][4][5]. In addition, a pancreatic organoid has been created by seeding adult mouse islets into the chamber, and the engineered islet graft effectively reduced blood glucose in type 1 diabetic mice [6]. Further, using neonatal rat cardiomyocytes in the rat chamber system, 3-dimensional strips of myocardial tissue have been created, which displayed contractions with intrinsic rhythms and could be paced, as well as producing positive chronotropic and inotropic responses in vitro to stretch, calcium and ␤-adrenoceptor agonists [7].Survival of the transplanted cells and the resulting tissue grafts in the TE chamber largely depends on the establishment of a functional vasculature capable of delivering sufficient oxygen and nutrients.…”

Strategies in cardiac tissue engineering

“…It was later discovered that this ‘wound healing’ environment provides a highly intense environment of angiogenesis, which allowed various implanted cells to survive within it 98–100 . To date, using this intrinsic vascularization technique, constructs consisting of either hepatocytes, pancreas, 101 myoblasts, 99 adipose tissue 100 and CMs 20 have been engineered. Other groups have also used this model to engineer bone tissue 102,103 and a similar model in mice utilizing a pedicle flow‐through configuration has been developed, 104 which subsequently became the main model for adipose tissue engineering at our institute 100,105 …”