Strategies for preventing porcine xenograft rejection: recent progress and future developments

被引:3
作者
Dorling, A
机构
[1] Imperial School of Science, Technology and Medicine, Hammersmith Campus, London W12 ONN, Du Cane Road
关键词
transgenic pigs; xenograft rejection; xenotransplantation;
D O I
10.1517/13543776.7.11.1307
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Interest in xenotransplantation (the use of animal organs for transplantation) has been revived because of the severe shortage of human donor organs, and pigs are currently thought to be the species most suitable for widespread use. Recent insights into the mechanisms underlying vascular rejection, endothelial cell activation and cellular responses to xenogeneic tissue have led to the development of novel methods designed to inhibit immune-mediated xenograft rejection. The first clinical trials of porcine organs are expected within the next few years, once outstanding questions about the safety of transplanted pig tissues have been addressed. They will herald a new era in medical practice, characterised by the practical application of modern molecular and genetic techniques to solve clinical problems. In the future, it is hoped that these same techniques may resolve some of the problems currently associated with long-term systemic immunosuppression and serve to inhibit the progress of chronic rejection, the process that currently limits the lifespan of transplanted allografts. This article reviews the pathophysiology of xenograft rejection and highlights the novel strategies to prevent hyperacute xenograft rejection that are likely to be useful in clinical practice. Other strategies designed to inhibit later stages of xenograft rejection are also presented, with emphasis on the need for graft-specific of 'tailored' immunosuppression. Areas where future development is likely are also discussed.
引用
收藏
页码:1307 / 1319
页数:13
相关论文
共 141 条
[1]  
*ADV GROUP ETH XEN, 1997, AN TISS HUM
[2]  
AKAMI T, 1993, TRANSPLANT P, V25, P394
[3]   Accommodation of vascularized xenografts: Expression of ''protective genes'' by donor endothelial cells in a host Th2 cytokine environment [J].
Bach, FH ;
Ferran, C ;
Hechenleitner, P ;
Mark, W ;
Koyamada, N ;
Miyatake, T ;
Winkler, H ;
Badrichani, A ;
Candinas, D ;
Hancock, WW .
NATURE MEDICINE, 1997, 3 (02) :196-204
[4]   Delayed xenograft rejection [J].
Bach, FH ;
Winkler, H ;
Ferran, C ;
Hancock, WW ;
Robson, SC .
IMMUNOLOGY TODAY, 1996, 17 (08) :379-384
[5]  
BACH FH, 1993, XENO, V1, P8
[6]  
Batten P, 1996, IMMUNOLOGY, V87, P127
[7]  
BIANCHI G, 1993, J IMMUNOL, V151, P5135
[8]   ACTIVATION OF INTRAGRAFT ENDOTHELIAL AND MONONUCLEAR-CELLS DURING DISCORDANT XENOGRAFT REJECTION [J].
BLAKELY, ML ;
VANDERWERF, WJ ;
BERNDT, MC ;
DALMASSO, AP ;
BACH, FH ;
HANCOCK, WW .
TRANSPLANTATION, 1994, 58 (10) :1059-1066
[9]   BLOCKADE OF THE CD28 COSTIMULATORY PATHWAY - A MEANS TO INDUCE TOLERANCE [J].
BOUSSIOTIS, VA ;
GRIBBEN, JG ;
FREEMAN, GJ ;
NADLER, LM .
CURRENT OPINION IN IMMUNOLOGY, 1994, 6 (05) :797-807
[10]  
BRAUER RB, 1993, J IMMUNOL, V151, P7240