Islet microencapsulation: a review

Abstract

The original report on the microencapsulation of islets of Langerhans used sodium alginate and poly-L-lysine (PLL) to form the capsules. Although several alternative materials have subsequently been used with vary-mg degrees of success, it is those studies using islets encapsulated in alginate-PLL-alginate which are reviewed in detail in this article. Since the first report of islet microencapsulation, many studies have demonstrated excellent in vitro viability of encapsulated islets. However, transplantation experiments into chemically induced diabetic recipients have yielded varied results, with some studies showing good long-term graft function whilst in others grafts failed due to pericapsular fibrosis. The use of naturally occurring animal models of type 1 (insulin-dependent) diabetes has demonstrated a decline in graft function, suggesting that this presents a more complex problem to be solved than that in chemically induced diabetic recipients. Fibrosis of capsules has been the major problem causing graft failure, and this has been demonstrated to be more severe in spontaneously diabetic models. However, recent advances in alginate purification and attempts to reduce the size of the encapsulated islets are major steps towards encapsulated islet transplants becoming a viable proposition for the treatment of type 1 diabetic patients.

Biocompatibility and physicochemical characteristics of alginate–polycation microcapsules

“…In the case of inadequate biocompatibility, the release of cytokines from nearby activated macrophages, cellular overgrowth and the development of fibrotic tissue surrounding the implant contribute greatly to encapsulated graft failure [7][8][9]. While at least one group has demonstrated that it is possible to produce alginate-polycation microcapsules that induce a minimal immune response [10], first-hand experience and an overview of published works indicate that such promising results are difficult to reproduce, despite the use of similar capsule structures [11,12].…”

Durability of sodium sulfate-treated polylysine-alginate microcapsules

“…[3][4][5][6][7] Several modalities have been developed to shield transplanted islets from the immune system, including macroencapsulation and microencapsulation methods. 8,9 Although microencapsulation has significant advantages over other methods of immunoisolation, and has shown some promise as a viable option for the treatment of diabetes, such as control of the diabetic state in several studies, 9 there are still some limiting factors to the use of the microcapsules, including capsule instability. 8,10,11 One factor contributing to the instability of the alginate microcapsules is a tendency toward capsule swelling as a result of their hygroscopic nature.…”

“…8,9 Although microencapsulation has significant advantages over other methods of immunoisolation, and has shown some promise as a viable option for the treatment of diabetes, such as control of the diabetic state in several studies, 9 there are still some limiting factors to the use of the microcapsules, including capsule instability. 8,10,11 One factor contributing to the instability of the alginate microcapsules is a tendency toward capsule swelling as a result of their hygroscopic nature. This hygroscopic tendency is associated with the presence of divalent cations such as Ca ++ , and the composition, block structure, and molecular size of the alginate molecules.…”

Long-Term Graft Function of Adult Rat and Human Islets Encapsulated in Novel Alginate-Based Microcapsules After Transplantation in Immunocompetent Diabetic Mice

“…Most importantly, graft survival is random and generally too limited for therapeutic application of these microcapsules (8 -10). The reasons for this are presumably the cytotoxicity of the polyamino acid and the mechanical instability of the microcapsules (2,11,12). Microcapsules made of alginate cross-linked with Ba 2ϩ do not share these disadvantages (13).…”