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Survival of human islets in microbeads containing high guluronic acid alginate crosslinked with Ca 2+ and Ba 2+

2012; Wiley; Volume: 19; Issue: 6 Linguagem: Inglês

10.1111/xen.12009

1399-3089

Meirigeng Qi, Ýrr Mørch, Igor Lacı́k, Kjetil Formo, Enza Marchese, Yong Wang, Kirstie K. Danielson, Katie Kinzer, Shusen Wang, Barbara Barbaro, Gabriela Kolláriková, D. Chorvát, David Hunkeler, Gudmund Skjåk‐Bræk, José Oberholzer, Berit L. Strand,

Diabetes and associated disorders

Qi M, Mørch Y, Lacík I, Formo K, Marchese E, Wang Y, Danielson KK, Kinzer K, Wang S, Barbaro B, Kolláriková G, Chorvát D Jr, Hunkeler D, Skjåk‐Bræk G, Oberholzer J, Strand BL. Survival of human islets in microbeads containing high guluronic acid alginate crosslinked with Ca 2+ and Ba 2+ . 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 Ca 2+ /Ba 2+ –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 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.