Islet xenotransplantation using gal-deficient neonatal donors improves engraftment and function.
Islet xenotransplantation using gal-deficient neonatal donors improves engraftment and function.
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DOI：
10.1111/j.1600-6143.2011.03720.x
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Kirk AD
中科院分区：
文献类型：
--
作者：
Thompson P;Badell IR;Lowe M;Cano J;Song M;Leopardi F;Avila J;Ruhil R;Strobert E;Korbutt G;Rayat G;Rajotte R;Iwakoshi N;Larsen CP;Kirk AD
Significant deficiencies in understanding of xenospecific immunity have impeded the success of preclinical trials in xenoislet transplantation. While galactose-α1,3-galactose, the gal epitope, has emerged as the principal target of rejection in pig-to-primate models of solid organ transplant, the importance of gal-specific immunity in islet xenotransplant models has yet to be clearly demonstrated. Here we directly compare the immunogenicity, survival and function of neonatal porcine islets (NPIs) from gal-expressing wild-type (WT) or gal-deficient galactosyl transferase knock-out (GTKO) donors. Paired diabetic rhesus macaques were transplanted with either WT (n=5) or GTKO (n=5) NPIs. Recipient blood glucose, transaminase, and serum xenoantibody levels were used to monitor response to transplant. Four of 5 GTKO versus 1 of 5 WT recipients achieved insulin-independent normoglycemia; transplantation of WT islets resulted in significantly greater transaminitis. WT NPIs were more susceptible to antibody and complement binding and destruction in vitro. Our results confirm that gal is an important variable in xenoislet transplantation. GTKO NPI recipients have improved rates of normoglycemia, likely due to decreased susceptibility of xenografts to innate immunity mediated by complement and preformed xenoantibody. Therefore, the use of GTKO donors is an important step towards improved consistency and interpretability of results in future xenoislet studies.
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影响因子：
4
作者：
Rayat, GR;Rajotte, RV;Korbutt, GS
通讯作者：
Korbutt, GS
DOI：
10.1073/pnas.90.23.11391
发表时间：
1993-12-01
影响因子：
11.1
作者：
SANDRIN, MS;VAUGHAN, HA;MCKENZIE, IFC
通讯作者：
MCKENZIE, IFC
影响因子：
3.9
作者：
Bühler, L;Deng, S;Morel, P
通讯作者：
Morel, P
影响因子：
6.2
作者：
Rood, Pleunie P. M.;Bottino, Rita;Trucco, Massimo
通讯作者：
Trucco, Massimo
影响因子：
82.9
作者：
Cardona, K;Korbutt, GS;Larsen, CP
通讯作者：
Larsen, CP