Correction of diabetic nod mice with insulinomas implanted within Baxter immunoisolation devices

Abstract

Insulin replacement by injection is clearly not a cure for Insulin Dependent Diabetes Mellitus (IDDM). Replacement of the destroyed islets by pancreas or islet allograft transplantation can achieve the good metabolic control required to prevent diabetic complications, but tissue supply is limited. The problem of islet supply to treat the 1 million IDDM patients in the USA could be overcome by using immortalized islet beta-cells as a donor source. However, before either allogeneic or xenogeneic immortalized beta-cells are used, some major problems have to be overcome: control of immortalized cell growth, allograft or xenograft rejection and recurrence of autoimmunity. To tackle these problems we have used a cell impermeable immunoisolation device containing mouse insulinoma cells. Transplantation of devices with insulinomas from NOD mice carrying the Rat-insulin promoter regulated SV40 T-Antigen transgene (RIP-TAg), normalized the blood glucose levels of diabetic NOD mice. Insulinomas from allogeneic CBA/NOD-RIP-TAg mice were also capable of normalizing diabetic NOD mice. Not only were non-fasting blood glucoses normalized but when given an intraperitoneal injection of glucose, the corrected mice had a near normal clearance of glucose from the blood. When the devices were removed from normalized mice they became diabetic again, demonstrating that the immunoisolation device was capable of protecting against both alloimmune and autoimmune destruction. The results with allogeneic mouse beta-cells suggest the possibility that immortalized human beta-cells could be an effective source of tissue to correct diabetes in IDDM patients without the use of immunosuppression.

Cell Viability and Noninvasive In Vivo MRI Tracking of 3D Cell Encapsulating Self-Assembled Microcontainers

“…Here we encapsulated cells within the microcontainer, which was then implanted in a severe combined controlled owing to polymer tortuosity (3, 16). Microel-404 GIMI ET AL.…”

Complete Protection of Islets Against Allorejection and Autoimmunity by a Simple Barium-Alginate Membrane

“…This accumulation of cells could be due to an immune response to the contained islets or to bioincompatibility of the capsular materials (16,17). Failure might also be attributed to problems with ␤-cell viability in the capsules (18).Protection of porcine islets remains a goal of encapsulation, but xenografts might be more difficult to protect than allografts, as suggested by studies performed with permeable polymer membranes (19,20). This concept is important because of the improved prospects for obtaining an abundant supply of human ␤-cells from precursor cells (21,22).…”

“…Protection of porcine islets remains a goal of encapsulation, but xenografts might be more difficult to protect than allografts, as suggested by studies performed with permeable polymer membranes (19,20). This concept is important because of the improved prospects for obtaining an abundant supply of human ␤-cells from precursor cells (21,22).…”

Treatment of Diabetes with Encapsulated Islets

“…The macrocapsules can be implanted in different sites such as the peritoneal cavity, [45][46][47][48] the subcutaneous site, [49][50][51][52][53][54][55] or the renal capsule. 56 The geometry of macrocapsules varies.…”