Survival of human islets in microbeads containing high guluronic acid alginate crosslinked with Ca2+and Ba2+

Qi M, Morch Y, Lacik I, Formo K, Marchese E, Wang Y, Danielson KK, Kinzer K, Wang S, Barbaro B, Kollarikova G, Chorvat D Jr, Hunkeler D, Skjak-Braek G, Oberholzer J, Strand BL. Survival of human islets in microbeads containing high guluronic acid alginate crosslinked with Ca2+ and Ba2+. Xenotransplantation 2012; 19: 355–364. © 2012 John Wiley & Sons A/S. Abstract: Background: The main hurdles to the widespread use of islet transplantation for the treatment of type 1 diabetes continue to be the insufficient number of appropriate donors and the need for immunosuppression. Microencapsulation has been proposed as a means to protect transplanted islets from the host’s immune system. Methods: This study investigated the function of human pancreatic islets encapsulated in Ca2+/Ba2+–alginate microbeads intraperitoneally transplanted in diabetic Balb/c mice. Results: All mice transplanted with encapsulated human islets (n = 29), at a quantity of 3000 islet equivalent (IEQ), achieved normoglycemia 1 day after transplantation and retained normoglycemia for extended periods of time (mean graft survival 134 ± 17 days). In comparison, diabetic Balb/c mice transplanted with an equal amount of non-encapsulated human islets rejected the islets within 2 to 7 days after transplantation (n = 5). Microbeads retrieved after 232 days (n = 3) were found with little to no fibrotic overgrowth and contained viable insulin-positive islets. Immunofluorescent staining on the retrieved microbeads showed F4/80-positive macrophages and alpha smooth muscle actin–positive fibroblasts but no CD3-positive T lymphocytes. Conclusions: The Ca2+/Ba2+–alginate microbeads can protect human islets from xenogeneic rejection in immunocompetent mice without immunosuppression. However, grafts ultimately failed likely secondary to a macrophage-mediated foreign body reaction.