異種器官移植的新進展_《中國普外基礎與臨床雜志》

作者：

杜冰清 , 麥剛 , 陳擁華 , 向光明 , 龔軍 , 鄭振江

四川大學華西醫院肝膽胰外科(成都 610041);

關鍵詞：

異種移植超急性排斥反應急性排斥反應慢性排斥反應轉基因豬異種耐受

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目的　總結異種器官移植的新進展。
方法　分析近年來異種器官移植進展的文獻報道。
結果　隨著免疫生物學的深入研究，異種器官移植取得了長足的進步，并開始應用于臨床,但免疫排斥反應的諸多問題仍在探尋之中。
結論　異種移植為解決器官衰竭患者移植器官短缺的問題展現了廣闊的前景，如何更有效地抑制排斥反應及延長移植物生存期是今后研究的重點。

引用本文： 杜冰清,麥剛,陳擁華,向光明,龔軍,鄭振江. 異種器官移植的新進展. 中國普外基礎與臨床雜志, 2010, 17(4): 338-342. doi: 復制

1.	Matsunari H, Nagashima H. Application of genetically modified and cloned pigs in translational research [J]. J Reprod Dev, 2009; 55(3): 225-230.
2.	Yang YG, Sykes M. Xenotransplantation: current status and a perspective on the future [J]. Nat Rev Immunol, 2007; 7(7): 519-531.
3.	Niemann H, Verhoeyen E, Wonigeit K, et al. Cytomegalovirus early promoter induced expression of hCD59 in porcine organs provides protection against hyperacute rejection [J]. Transplantation, 2001; 72(12): 1898-1906.
4.	Kolber-Simonds D, Lai L, Watt SR, et al. Production of α-1,3-galactosyltransferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations [J]. Proc Natl Acad Sci USA, 2004; 101(19): 7335-7340.
5.	Yang YG, Sykes M. Xenotransplantation: current status and a perspective on the future [J]. Nat Rev Immunol, 2007; 7(7): 519-531.
6.	Lin CC, Cooper DK, Dorling A. Coagulation dysregulation as a barrier to xenotransplantation in the primate [J]. Transpl Immunol, 2009; 21(2): 75-80.
7.	Sprangers B, Waer M, Billiau AD. Xenotransplantation: where are we in 2008? [J]. Kidney Int, 2008; 74(1): 14-21.
8.	Cadili A, Kneteman N. The role of macrophages in xenograft rejection [J]. Transplant Proc, 2008; 40(10): 3289-3293.
9.	Maeda A, Goto M, Zhang J, et al. Immunosuppression with FTY720 and cyclosporine A inhibits rejection of adult porcine islet xenografts in rats [J]. Transplantation, 2003; 75(8): 1409-1414.
10.	Weiss MJ, Ng CY, Madsen JC. Tolerance, xenotransplantation: future therapies [J]. Surg Clin North Am, 2006; 86(5): 1277-1296.
11.	Ekser B, Cooper DK. Update: cardiac xenotransplantation [J]. Curr Opin Organ Transplant, 2008; 13(5): 531-535.
12.	Ma Y, He KM, Garcia B, et al. Adoptive transfer of double negative T regulatory cells induces B-cell death in vivo and alters rejection pattern of rat-to-mouse heart transplantation [J]. Xenotransplantation, 2008; 15(1): 56-63.
13.	Muller YD, Golshayan D, Ehirchiou D, et al. T regulatory cells in xenotransplantation [J]. Xenotransplantation, 2009; 16(3): 121-128.
14.	Weiss EH, Lilienfeld BG, Müller S, et al. HLA-E/human beta2-microglobulin transgenic pigs: protection against xenogeneic human anti-pig natural killer cell cytotoxicity [J]. Transplantation, 2009; 87(1): 35-43.
15.	Yi S, Hawthorne WJ, Lehnert AM, et al. T cell-activated macrophages are capable of both recognition and rejection of pancreatic islet xenografts [J]. J Immunol, 2003; 170(5): 2750-2758.
16.	Yi S, Ouyang L, Ha H, et al. Involvement of CCR5 signaling in macrophage recruitment to porcine islet xenografts [J]. Transplantation, 2005; 80(10): 1468-1475.
17.	Cowan PJ. Coagulation and the xenograft endothelium [J]. Xenotransplantation, 2007; 14(1): 7-12.
18.	Cowan PJ, Roussel JC, d’Apice AJ. The vascular and coagulation issues in xenotransplantation [J]. Curr Opin Organ Transplant, 2009; 14(2): 161-167.
19.	Crikis S, Cowan PJ, d’Apice AJ. Intravascular thrombosis in discordant xenotransplantation [J]. Transplantation, 2006; 82(9): 1119-1123.
20.	Cooper DK, Dorling A, Pierson RN 3rd, et al. Alpha 1,3-galactosyltransferase gene-knockout pigs for xenotransplantation: where do we go from here? [J]. Transplantation, 2007; 84(1): 1-7.
21.	Denner J. Is porcine endogenous retrovirus (PERV) transmission still relevant? [J]. Transplant Proc, 2008; 40(2): 587-589.
22.	Scobie L, Takeuchi Y. Porcine endogenous retrovirus and other viruses in xenotransplantation [J]. Curr Opin Organ Transplant, 2009; 14(2): 175-179.
23.	Hering BJ, Wijkstrom M, Graham ML, et al. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates [J]. Nat Med， 2006; 12(3): 301-303.
24.	Smith RM, Mandel TE. Pancreatic islet xenotransplantation: the potential for tolerance induction [J]. Immunol Today, 2000; 21(1): 42-48.
25.	Cardona K, Korbutt GS, Milas Z, et al. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways [J]. Nat Med, 2006; 12(3): 304-306.
26.	Kumagai-Braesch M, Ekberg H, Wang F, et al. Anti-LFA-1 improves pig islet xenograft function in diabetic mice when long-term acceptance is induced by CTLA4Ig/anti-CD40L [J]. Transplantation, 2007; 83(9): 1259-1267.
27.	Dufrane D, Goebbels RM, Saliez A, et al. Six-month survival of microencapsulated pig islets and alginate biocompatibility in primates: proof of concept [J]. Transplantation, 2006; 81(9): 1345-1353.
28.	Mayor S. Australian team to transplant pig islet cells into patients with unstable diabetes [J]. BMJ, 2009; 339: b3089.
29.	Casu A, Bottino R, Balamurugan AN, et al. Metabolic aspects of pig-to-monkey (Macaca fascicularis) islet transplantation: implications for translation into clinical practice [J]. Diabetologia, 2008; 51(1): 120-129.
30.	Zhu X, Dor FJ, Cooper DK. Pig-to-non-human primate heart transplantation: immunologic progress over 20 years [J]. J Heart Lung Transplant, 2007; 26(3): 210-218.
31.	Kuwaki K, Tseng YL, Dor FJ, et al. Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors: initial experience [J]. Nat Med, 2005; 11(1): 29-31.
32.	Hammerman MR. Xenotransplantation of renal primordial [J]. Curr Opin Nephrol Hypertens, 2002; 11(1): 11-16.
33.	Chen G, Qian H, Starzl T, et al. Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys [J]. Nat Med, 2005; 11(12): 1295-1298.
34.	Knosalla C, Yazawa K, Behdad A, et al. Renal and cardiac endothelial heterogeneity impact acute vascular rejection in pig-to-baboon xenotransplantation [J]. Am J Transplant, 2009; 9(5): 1006-1016.
35.	Yamada K, Yazawa K, Shimizu A, et al. Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue [J]. Nat Med, 2005; 11(1): 32-34.
36.	Ekser B, Rigotti P, Gridelli B, et al. Xenotransplantation of solid organs in the pig-to-primate model [J]. Transpl Immunol, 2009; 21(2): 87-92.
37.	Hara H, Gridelli B, Lin YJ, et al. Liver xenografts for the treatment of acute liver failure: clinical and experimental experience and remaining immunologic barriers [J]. Liver Transpl, 2008; 14(4): 425-434.
38.	Pascher A, Sauer IM, Hammer C, et al. Extracorporeal liver perfusion as hepatic assist in acute liver failure: a review of world experience [J]. Xenotransplantation, 2002; 9(5): 309-324.
39.	Horslen SP, Hammel JM, Fristoe LW, et al. Extracorporeal liver perfusion using human and pig livers for acute liver failure [J]. Transplantation， 2000; 70(10): 1472-1478.
40.	Tector AJ, Elias N, Rosenberg L, et al. Mechanisms of resistance to injury in pig livers perfused with blood from patients in liver failure [J]. Transplant Proc, 1997; 29(1-2): 966-969.
41.	Platt JL. Xenotransplantation of the liver: is more complement control needed? [J]. Liver Transpl, 2001; 7(10): 933-934.
42.	Rees MA, Butler AJ, Negus MC, et al. Classical pathway complement destruction is not responsible for the loss of human erythrocytes during porcine liver perfusion [J]. Transplantation, 2004; 77(9): 1416-1423.
43.	Oldenborg PA, Zheleznyak A, Fang YF, et al. Role of CD47 as a marker of self on red blood cells [J]. Science, 2000; 288(5473): 2051-2054.
44.	Tai HC, Zhu X, Hara H, et al. The pig-to-primate immune response: relevance for xenotransplantation [J]. Xenotransplantation, 2007; 14(3): 227-235.

1. Matsunari H, Nagashima H. Application of genetically modified and cloned pigs in translational research [J]. J Reprod Dev, 2009; 55(3): 225-230.
2. 　Yang YG, Sykes M. Xenotransplantation: current status and a perspective on the future [J]. Nat Rev Immunol, 2007; 7(7): 519-531.
3. 　Niemann H, Verhoeyen E, Wonigeit K, et al. Cytomegalovirus early promoter induced expression of hCD59 in porcine organs provides protection against hyperacute rejection [J]. Transplantation, 2001; 72(12): 1898-1906.
4. 　Kolber-Simonds D, Lai L, Watt SR, et al. Production of α-1,3-galactosyltransferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations [J]. Proc Natl Acad Sci USA, 2004; 101(19): 7335-7340.
5. 　Yang YG, Sykes M. Xenotransplantation: current status and a perspective on the future [J]. Nat Rev Immunol, 2007; 7(7): 519-531.
6. 　Lin CC, Cooper DK, Dorling A. Coagulation dysregulation as a barrier to xenotransplantation in the primate [J]. Transpl Immunol, 2009; 21(2): 75-80.
7. 　Sprangers B, Waer M, Billiau AD. Xenotransplantation: where are we in 2008? [J]. Kidney Int, 2008; 74(1): 14-21.
8. 　Cadili A, Kneteman N. The role of macrophages in xenograft rejection [J]. Transplant Proc, 2008; 40(10): 3289-3293.
9. 　Maeda A, Goto M, Zhang J, et al. Immunosuppression with FTY720 and cyclosporine A inhibits rejection of adult porcine islet xenografts in rats [J]. Transplantation, 2003; 75(8): 1409-1414.
10. 　Weiss MJ, Ng CY, Madsen JC. Tolerance, xenotransplantation: future therapies [J]. Surg Clin North Am, 2006; 86(5): 1277-1296.
11. 　Ekser B, Cooper DK. Update: cardiac xenotransplantation [J]. Curr Opin Organ Transplant, 2008; 13(5): 531-535.
12. 　Ma Y, He KM, Garcia B, et al. Adoptive transfer of double negative T regulatory cells induces B-cell death in vivo and alters rejection pattern of rat-to-mouse heart transplantation [J]. Xenotransplantation, 2008; 15(1): 56-63.
13. 　Muller YD, Golshayan D, Ehirchiou D, et al. T regulatory cells in xenotransplantation [J]. Xenotransplantation, 2009; 16(3): 121-128.
14. 　Weiss EH, Lilienfeld BG, Müller S, et al. HLA-E/human beta2-microglobulin transgenic pigs: protection against xenogeneic human anti-pig natural killer cell cytotoxicity [J]. Transplantation, 2009; 87(1): 35-43.
15. 　Yi S, Hawthorne WJ, Lehnert AM, et al. T cell-activated macrophages are capable of both recognition and rejection of pancreatic islet xenografts [J]. J Immunol, 2003; 170(5): 2750-2758.
16. 　Yi S, Ouyang L, Ha H, et al. Involvement of CCR5 signaling in macrophage recruitment to porcine islet xenografts [J]. Transplantation, 2005; 80(10): 1468-1475.
17. 　Cowan PJ. Coagulation and the xenograft endothelium [J]. Xenotransplantation, 2007; 14(1): 7-12.
18. 　Cowan PJ, Roussel JC, d’Apice AJ. The vascular and coagulation issues in xenotransplantation [J]. Curr Opin Organ Transplant, 2009; 14(2): 161-167.
19. 　Crikis S, Cowan PJ, d’Apice AJ. Intravascular thrombosis in discordant xenotransplantation [J]. Transplantation, 2006; 82(9): 1119-1123.
20. 　Cooper DK, Dorling A, Pierson RN 3rd, et al. Alpha 1,3-galactosyltransferase gene-knockout pigs for xenotransplantation: where do we go from here? [J]. Transplantation, 2007; 84(1): 1-7.
21. 　Denner J. Is porcine endogenous retrovirus (PERV) transmission still relevant? [J]. Transplant Proc, 2008; 40(2): 587-589.
22. 　Scobie L, Takeuchi Y. Porcine endogenous retrovirus and other viruses in xenotransplantation [J]. Curr Opin Organ Transplant, 2009; 14(2): 175-179.
23. 　Hering BJ, Wijkstrom M, Graham ML, et al. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates [J]. Nat Med， 2006; 12(3): 301-303.
24. 　Smith RM, Mandel TE. Pancreatic islet xenotransplantation: the potential for tolerance induction [J]. Immunol Today, 2000; 21(1): 42-48.
25. 　Cardona K, Korbutt GS, Milas Z, et al. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways [J]. Nat Med, 2006; 12(3): 304-306.
26. 　Kumagai-Braesch M, Ekberg H, Wang F, et al. Anti-LFA-1 improves pig islet xenograft function in diabetic mice when long-term acceptance is induced by CTLA4Ig/anti-CD40L [J]. Transplantation, 2007; 83(9): 1259-1267.
27. 　Dufrane D, Goebbels RM, Saliez A, et al. Six-month survival of microencapsulated pig islets and alginate biocompatibility in primates: proof of concept [J]. Transplantation, 2006; 81(9): 1345-1353.
28. 　Mayor S. Australian team to transplant pig islet cells into patients with unstable diabetes [J]. BMJ, 2009; 339: b3089.
29. 　Casu A, Bottino R, Balamurugan AN, et al. Metabolic aspects of pig-to-monkey (Macaca fascicularis) islet transplantation: implications for translation into clinical practice [J]. Diabetologia, 2008; 51(1): 120-129.
30. 　Zhu X, Dor FJ, Cooper DK. Pig-to-non-human primate heart transplantation: immunologic progress over 20 years [J]. J Heart Lung Transplant, 2007; 26(3): 210-218.
31. 　Kuwaki K, Tseng YL, Dor FJ, et al. Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors: initial experience [J]. Nat Med, 2005; 11(1): 29-31.
32. 　Hammerman MR. Xenotransplantation of renal primordial [J]. Curr Opin Nephrol Hypertens, 2002; 11(1): 11-16.
33. 　Chen G, Qian H, Starzl T, et al. Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys [J]. Nat Med, 2005; 11(12): 1295-1298.
34. 　Knosalla C, Yazawa K, Behdad A, et al. Renal and cardiac endothelial heterogeneity impact acute vascular rejection in pig-to-baboon xenotransplantation [J]. Am J Transplant, 2009; 9(5): 1006-1016.
35. 　Yamada K, Yazawa K, Shimizu A, et al. Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue [J]. Nat Med, 2005; 11(1): 32-34.
36. 　Ekser B, Rigotti P, Gridelli B, et al. Xenotransplantation of solid organs in the pig-to-primate model [J]. Transpl Immunol, 2009; 21(2): 87-92.
37. 　Hara H, Gridelli B, Lin YJ, et al. Liver xenografts for the treatment of acute liver failure: clinical and experimental experience and remaining immunologic barriers [J]. Liver Transpl, 2008; 14(4): 425-434.
38. 　Pascher A, Sauer IM, Hammer C, et al. Extracorporeal liver perfusion as hepatic assist in acute liver failure: a review of world experience [J]. Xenotransplantation, 2002; 9(5): 309-324.
39. 　Horslen SP, Hammel JM, Fristoe LW, et al. Extracorporeal liver perfusion using human and pig livers for acute liver failure [J]. Transplantation， 2000; 70(10): 1472-1478.
40. 　Tector AJ, Elias N, Rosenberg L, et al. Mechanisms of resistance to injury in pig livers perfused with blood from patients in liver failure [J]. Transplant Proc, 1997; 29(1-2): 966-969.
41. 　Platt JL. Xenotransplantation of the liver: is more complement control needed? [J]. Liver Transpl, 2001; 7(10): 933-934.
42. 　Rees MA, Butler AJ, Negus MC, et al. Classical pathway complement destruction is not responsible for the loss of human erythrocytes during porcine liver perfusion [J]. Transplantation, 2004; 77(9): 1416-1423.
43. 　Oldenborg PA, Zheleznyak A, Fang YF, et al. Role of CD47 as a marker of self on red blood cells [J]. Science, 2000; 288(5473): 2051-2054.
44. 　Tai HC, Zhu X, Hara H, et al. The pig-to-primate immune response: relevance for xenotransplantation [J]. Xenotransplantation, 2007; 14(3): 227-235.

《中國普外基礎與臨床雜志》

異種器官移植的新進展

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

《中國普外基礎與臨床雜志》

異種器官移植的新進展

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料