Recent advances in understanding xenotransplantation: implications for the clinic

被引:32
作者
Cooper, David K. C. [1 ]
Bottino, Rita [2 ]
机构
[1] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA
[2] Allegheny Singer Res Inst, Inst Cellular Therapeut, Pittsburgh, PA 15212 USA
关键词
genetically-engineered pig; immunobiology; islets pig; organs pig; xenotransplantation; MACROPHAGE-MEDIATED CYTOTOXICITY; CARDIAC XENOGRAFT SURVIVAL; DIABETIC NONHUMAN-PRIMATES; N-GLYCOLYLNEURAMINIC ACID; THYROID-HORMONE THERAPY; GENE-KNOCKOUT PIGS; ISLET XENOTRANSPLANTATION; COSTIMULATION BLOCKADE; HUMAN THROMBOMODULIN; THROMBOTIC MICROANGIOPATHY;
D O I
10.1586/1744666X.2015.1083861
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The results of organ and cell allotransplantation continue to improve, but the field remains limited by a lack of deceased donor organs. Xenotransplantation, for example, between pig and human, offers unlimited organs and cells for clinical transplantation. The immune barriers include a strong innate immune response in addition to the adaptive T-cell response. The innate response has largely been overcome by the transplantation of organs from pigs with genetic modifications that protect their tissues from this response. T-cell-mediated rejection can be controlled by immunosuppressive agents that inhibit costimulation. Coagulation dysfunction between the pig and primate remains problematic but is being overcome by the transplantation of organs from pigs that express human coagulation-regulatory proteins. The remaining barriers will be resolved by the introduction of novel genetically-engineered pigs. Limited clinical trials of pig islet and corneal transplantation are already underway.
引用
收藏
页码:1379 / 1390
页数:12
相关论文
共 102 条
[1]   Regenerative Medicine [J].
Atala, Anthony ;
Murphy, Sean .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2015, 313 (14) :1413-1414
[2]  
Azimzadeh A, 2015, XENOTRANSPLANTATION
[3]   Clearance of mobilized porcine peripheral blood progenitor cells is delayed by depletion of the pragocytic reticuloendothelial system in baboons [J].
Basker, M ;
Alwayn, IPJ ;
Buhler, L ;
Harper, D ;
Abraham, S ;
Gray, HK ;
DeAngelis, H ;
Awwad, M ;
Down, J ;
Rieben, R ;
White-Scharf, ME ;
Sachs, DH ;
Thall, A ;
Cooper, DKC .
TRANSPLANTATION, 2001, 72 (07) :1278-1285
[4]   Pig-to-Monkey Islet Xenotransplantation Using Multi-Transgenic Pigs [J].
Bottino, R. ;
Wijkstrom, M. ;
van der Windt, D. J. ;
Hara, H. ;
Ezzelarab, M. ;
Murase, N. ;
Bertera, S. ;
He, J. ;
Phelps, C. ;
Ayares, D. ;
Cooper, D. K. C. ;
Trucco, M. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2014, 14 (10) :2275-2287
[5]   Simultaneous expression by porcine aorta endothelial cells of glycosphingolipids bearing the major epitope for human xenoreactive antibodies (Gal alpha 1-3Gal), blood group H determinant and N-glycolylneuraminic acid [J].
Bouhours, D ;
Pourcel, C ;
Bouhours, JF .
GLYCOCONJUGATE JOURNAL, 1996, 13 (06) :947-953
[6]  
Bühler L, 2000, TRANSPLANTATION, V69, P2296
[7]   Expression of Human CD46 Modulates Inflammation Associated With GalTKO Lung Xenograft Injury [J].
Burdorf, L. ;
Stoddard, T. ;
Zhang, T. ;
Rybak, E. ;
Riner, A. ;
Avon, C. ;
Laaris, A. ;
Cheng, X. ;
Sievert, E. ;
Braileanu, G. ;
Newton, A. ;
Phelps, C. J. ;
Ayares, D. ;
Azimzadeh, A. M. ;
Pierson, R. N., III .
AMERICAN JOURNAL OF TRANSPLANTATION, 2014, 14 (05) :1084-1095
[8]   Reduced Binding of Human Antibodies to Cells From GGTA1/CMAH KO Pigs [J].
Burlak, C. ;
Paris, L. L. ;
Lutz, A. J. ;
Sidner, R. A. ;
Estrada, J. ;
Li, P. ;
Tector, M. ;
Tector, A. J. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2014, 14 (08) :1895-1900
[9]   Cloning and expression of porcine β1,4 N-acetylgalactosaminyl transferase encoding a new xenoreactive antigen [J].
Byrne, Guerard W. ;
Du, Zeji ;
Stalboerger, Paul ;
Kogelberg, Heide ;
McGregor, Christopher G. A. .
XENOTRANSPLANTATION, 2014, 21 (06) :543-554
[10]   Engraftment of adult porcine islet xenografts in diabetic nonhuman primates through targeting of costimulation pathways [J].
Cardona, K. ;
Milas, Z. ;
Strobert, E. ;
Cano, J. ;
Jiang, W. ;
Safley, S. A. ;
Gangappa, S. ;
Hering, B. J. ;
Weber, C. J. ;
Pearson, T. C. ;
Larsen, C. P. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2007, 7 (10) :2260-2268