Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates.
Cell-based diabetes therapy requires an abundant cell source. Here, we report reversal of diabetes for more than 100 d in cynomolgus macaques after intraportal transplantation of cultured islets from genetically unmodified pigs without Gal-specific antibody manipulation. Immunotherapy with CD25-specific and CD154-specific monoclonal antibodies, FTY720 (or tacrolimus), everolimus and leflunomide suppressed indirect activation of T cells, elicitation of non-Gal pig-specific IgG antibody, intragraft expression of proinflammatory cytokines and invasion of infiltrating mononuclear cells into islets.
Diabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, 424 Harvard Street SE, Minneapolis, Minnesota 55455, USA. bhering@umn.edu
Bernhard J
BJ
Hering
Martin
M
Wijkstrom
Melanie L
ML
Graham
Maria
M
Hårdstedt
Tor C
TC
Aasheim
Tun
T
Jie
Jeffrey D
JD
Ansite
Masahiko
M
Nakano
Jane
J
Cheng
Wei
W
Li
Kathleen
K
Moran
Uwe
U
Christians
Colleen
C
Finnegan
Charles D
CD
Mills
David E
DE
Sutherland
Pratima
P
Bansal-Pakala
Michael P
MP
Murtaugh
Nicole
N
Kirchhof
Henk-Jan
HJ
Schuurman
D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000276:immunology / Q000601:surgery*; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D007165:Immunosuppression Therapy; D007515:Islets of Langerhans / Q000166:cytology; D016381:Islets of Langerhans Transplantation; D008251:Macaca / Q000276:immunology* / Q000601:surgery*; D011168:Portal System / Q000276:immunology; D013552:Swine; D014183:Transplantation, Heterologous