Islet transplantation in rodents: do encapsulated islets really work?

Abstract

-Context -Diabetes mellitus type I affects around 240 million people in the world and only in the USA 7.8% of the population.It has been estimated that the costs of its complications account for 5% to 10% of the total healthcare spending around the world. According to World Health Organization, 300 million people are expected to develop diabetes mellitus by the year 2025. The pancreatic islet transplantation is expected to be less invasive than a pancreas transplant, which is currently the most commonly used approach. Objectives -To compare the encapsulated and free islet transplantation in rodents looking at sites of islet implantation, number of injected islets, viability and immunosuppression. Methods -A literature search was conducted using MEDLINE/PUBMED and SCIELO with terms about islet transplantation in the rodent from 2000 to 2010. We found 2,636 articles but only 56 articles from 2000 to 2010 were selected. Results -In these 56 articles used, 34% were encapsulated and 66% were nonencapsulated islets. Analyzing both types of islets transplantation, the majority of the encapsulated islets were implanted into the peritoneal cavity and the nonencapsulated islets into the liver, through the portal vein. In addition, the great advantage of the peritoneal cavity as the site of islet transplantation is its blood supply. Both vascular endothelial cells and vascular endothelial growth factor were used to stimulate angiogenesis of the islet grafts, increasing the vascularization rapidly after implantation. It also has been proven that there is influence of the capsules, since the larger the capsule more chances there are of central necrosis. In some articles, the use of immunosuppression demonstrated to increase the life expectancy of the graft. Conclusion -While significant progress has been made in the islets transplantation field, many obstacles remain to be overcome. Microencapsulation provides a means to transplant islets without immunosuppressive agents and may enable the performance of xenotransplantation. The use of alternative donor sources, fewer islets per capsule and the appropriate deployment location, such as the peritoneal cavity, may give a future perspective to the application of immunoprotective capsules and viability in clinical practice. A variety of strategies, such as genetic engineering, co-encapsulation, improvement in oxygen supply or the establishment of hypoxia resistance will also improve the islet transplantation performance. It remains to be determined which combination of strategies with encapsulation can fulfill the promise of establishing a simple and safe transplantation as a cure for diabetes.

Device design and materials optimization of conformal coating for islets of Langerhans

“…Immunoisolation via cell encapsulation may allow transplantation without SI and increase the safety and clinical impact of the procedure (2)(3)(4)(5). Although encapsulation has been studied for the past 50 y (6), its clinical success, thus far, has been limited (2,4,(7)(8)(9)(10)(11)(12). Among the possible reasons for the failure of immunoisolation technologies are the large size (between 600 μm and 3 mm), which results in diffusional gradients and large implant volumes, and the instability of conventional encapsulation materials.…”

Mold‐casted non‐degradable, islet macro‐encapsulating hydrogel devices for restoration of normoglycemia in diabetic mice

“…The approach investigated herein employs hydrogel encapsulation that has been implemented with numerous microencapsulation strategies, yet also creates a 3D implantable structure that aims to create a defined site in vivo for cell delivery. Among the hydrogels employed for encapsulation, alginate microcapsules are the most common, which have demonstrated engraftment and function in rodent models with transplantation of islets able to maintain euglycemia for times typically on the order of 75 days, though some reports have demonstrated function for much longer times (de Souza et al, ) . However, alginate microcapsules have had limited efficacy in larger animal models (Buder et al, ; de Souza et al, ).…”

Bioengineering the Pancreas: Cell-on-Scaffold Technology

“…In all these settings several strategies have been tested including capsule customization with three particular molecules such as the alginate, the glucoronic and mannuronic acids, which if used (or combined with other mono/polymer(s)) [70] can confer more strength and stability. Rodent preclinical models are the most studied, as reviewed by Souza et al who have evaluated more than 60 encapsulation strategies and have founded that the most effective approach is based on the use of intraperitoneal alginate-base microencapsulation without immunosuppressive strategies (islets mean survival rate 100 days) and intraportal injection with immunosuppression (islets mean survival rate 164 days) [71]. Indeed, high mannuronic acid, as biomaterial for islets encapsulation, has shown prolonged survival rate for more than 350 days [72].…”