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

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

Xenotransplantation (2012-12-04)
Meirigeng Qi, Yrr Mørch, Igor Lacík, Kjetil Formo, Enza Marchese, Yong Wang, Kirstie K Danielson, Katie Kinzer, Shusen Wang, Barbara Barbaro, Gabriela Kolláriková, Dušan Chorvát, David Hunkeler, Gudmund Skjåk-Braek, José Oberholzer, Berit L Strand
要旨

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. This study investigated the function of human pancreatic islets encapsulated in Ca(2+) /Ba(2+) -alginate microbeads intraperitoneally transplanted in diabetic Balb/c mice. 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. The Ca(2+) /Ba(2+) -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.

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