Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates

被引:403
作者
Hering, BJ
Wijkstrom, M
Graham, ML
Hårstedt, M
Aasheim, TC
Jie, T
Ansite, JD
Nakano, M
Cheng, J
Li, W
Moran, K
Christians, U
Finnegan, C
Mills, CD
Sutherland, DE
Bansal-Pakala, P
Murtaugh, MP
Kirchhof, N
Schuurman, HJ
机构
[1] Univ Minnesota, Diabet Inst Immunol & Transplantat, Dept Surg, Minneapolis, MN 55455 USA
[2] Immerge BioTherapeut Inc, Charlestown, MA 02129 USA
[3] Univ Colorado, Hlth Sci Ctr, Dept Anesthesia, Denver, CO 80262 USA
[4] Univ Minnesota, Dept Vet & Biomed Sci, St Paul, MN 55108 USA
[5] Univ Minnesota, Dept Vet Populat Med, Vet Med Ctr 225, St Paul, MN 55108 USA
关键词
D O I
10.1038/nm1369
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 GaI-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-GaI pig-specific IgG antibody, intragraft expression of proinflammatory cytokines and invasion of infiltrating mononuclear cells into islets.
引用
收藏
页码:301 / 303
页数:3
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