Survival of Microencapsulated Islets at 400 Days Posttransplantation in the Omental Pouch of NOD Mice

Abstract

The long-term durability of agarose microencapsulated islets against autoimmunity was evaluated in NOD mice. Islets were isolated from 6-8-week-old prediabetic male NOD mice and microencapsulated in 5% agarose hydrogel. Microencapsulated or nonencapsulated islets were transplanted into the omental pouch of spontaneously diabetic NOD mice. Although the diabetic NOD mice that received nonencapsulated islets experienced a temporary reversal of their hyperglycemic condition, all 10 of these mice returned to hyperglycemia within 3 weeks. In contrast, 9 of 10 mice transplanted with microencapsulated islets maintained normoglycemia for more than 100 days. Islet grafts were removed at 100, 150, 200, 300, and 400 days posttransplantation. A prompt return to hyperglycemia was observed in the mice after graft removal, indicating that the encapsulated islet grafts were responsible for maintaining euglycemia. Histological examination revealed viable islets in the capsules at all time points of graft removal. In addition, β-cells within the capsules remained well granulated as revealed by the immunohistochemical detection of insulin. No immune cells were detected inside the microcapsules and no morphological irregularities of the microcapsules were observed at any time point, suggesting that the microcapsules successfully protected the islets from cellular immunity. Sufficient vascularization was evident close to the microcapsules. Considerable numbers of islets showed central necrosis at 400 days posttransplantation, although the necrotic islets made up only a small percentage of the islet grafts. Islets with central necrosis also showed abundant insulin production throughout the entire islets, except for the necrotic part. These results demonstrate the long-term durability of agarose microcapsules against autoimmunity in a syngeneic islet transplantation model in NOD mice.

Employment of Microencapsulated Sertoli Cells as a New Tool to Treat Duchenne Muscular Dystrophy

“…A single i.p. injection of MC-SeC promoted body growth in a mouse model of the human Laron syndrome (dwarfism), characterized by mutations in GHR (growth Alginate-based microcapsules have shown long durability in terms of survival of the entrapped cells and have been used in rodents, dogs and monkeys [111][112][113][114]. Moreover, alginate-based microcapsules containing human pancreatic islets have been employed in clinical trials in which they were transplanted i.p.…”

Avoiding Immunosuppression for Islet Transplantation: Use of Protective Biomaterials

“…This study was repeated in 2006, where the same period of normoglycemia was observed in transplant recipients. In addition, when the devices were removed after 400 days, viable islets were recovered with a small percentage of necrotic cells [14]. Aside from agarose, polyethylene glycol-poly lactic-co-glycolic acid (PEG-PLGA) has been used to encapsulate 500-600 IEq islets for syngeneic transplant into streptozotocin (STZ) induced diabetic BALB/c mice, where over half of the recipients achieved normal glucose levels for up to 100 days [15].…”

Encapsulated islets transplantation: Past, present and future

“…For example, the alginate capsule is made by dropping it into ionic solution (Ca 2+ , Ba 2+ , etc.) [55] and the agarose capsule is made by cooling with shaking [56] . Microcapsules have some advantages in the transportation of oxygen and nutrients because of the smaller distance between the capsule surface and the islet [38] .…”

“…In experimental studies, there are many descriptions of positive data on extrahepatic transplantation sites. The Kyoto and other groups [73] succeeded in achieving normoglycemia in diabetic mice by transplantation of encapsulated islets in muscle, subcutaneous tissue [58,[74][75][76] , renal subcapsule [77] and omentum [56] . These may be candidate transplantation sites in the near future because the loss of islets due to IBMIR, the risk of portal hypertension and portal vein thrombosis could be prevented.…”