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.
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 humanpancreatic 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.
Authors: Bernhard J Hering; Martin Wijkstrom; Melanie L Graham; Maria Hårdstedt; Tor C Aasheim; Tun Jie; Jeffrey D Ansite; Masahiko Nakano; Jane Cheng; Wei Li; Kathleen Moran; Uwe Christians; Colleen Finnegan; Charles D Mills; David E Sutherland; Pratima Bansal-Pakala; Michael P Murtaugh; Nicole Kirchhof; Henk-Jan Schuurman Journal: Nat Med Date: 2006-02-19 Impact factor: 53.440
Authors: Mohammad Nourmohammadzadeh; Joe F Lo; Matt Bochenek; Joshua E Mendoza-Elias; Qian Wang; Ze Li; Liyi Zeng; Merigeng Qi; David T Eddington; José Oberholzer; Yong Wang Journal: Anal Chem Date: 2013-11-15 Impact factor: 6.986
Authors: Nadia Cobo-Vuilleumier; Petra I Lorenzo; Noelia García Rodríguez; Irene de Gracia Herrera Gómez; Esther Fuente-Martin; Livia López-Noriega; José Manuel Mellado-Gil; Silvana-Yanina Romero-Zerbo; Mathurin Baquié; Christian Claude Lachaud; Katja Stifter; German Perdomo; Marco Bugliani; Vincenzo De Tata; Domenico Bosco; Geraldine Parnaud; David Pozo; Abdelkrim Hmadcha; Javier P Florido; Miguel G Toscano; Peter de Haan; Kristina Schoonjans; Luis Sánchez Palazón; Piero Marchetti; Reinhold Schirmbeck; Alejandro Martín-Montalvo; Paolo Meda; Bernat Soria; Francisco-Javier Bermúdez-Silva; Luc St-Onge; Benoit R Gauthier Journal: Nat Commun Date: 2018-04-16 Impact factor: 14.919