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.
Hering
Bernhard J
BJ
Diabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, 424 Harvard Street SE, Minneapolis, Minnesota 55455, USA. bhering@umn.edu
Wijkstrom
Martin
M
Graham
Melanie L
ML
Hårdstedt
Maria
M
Aasheim
Tor C
TC
Jie
Tun
T
Ansite
Jeffrey D
JD
Nakano
Masahiko
M
Cheng
Jane
J
Li
Wei
W
Moran
Kathleen
K
Christians
Uwe
U
Finnegan
Colleen
C
Mills
Charles D
CD
Sutherland
David E
DE
Bansal-Pakala
Pratima
P
Murtaugh
Michael P
MP
Kirchhof
Nicole
N
Schuurman
Henk-Jan
HJ
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