Pig Liver Xenotransplantation: A Review of Progress Toward the Clinic

被引:40
作者
Cooper, David K. C. [1 ]
Dou, Ke-Feng [2 ]
Tao, Kai-shan [2 ]
Yang, Zhao-xu [2 ]
Tector, A. Joseph [3 ]
Ekser, Burcin [3 ]
机构
[1] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Starzl Biomed Sci Tower,W1543 200 Lothrop St, Pittsburgh, PA 15261 USA
[2] Fourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian, Shianxi, Peoples R China
[3] Indiana Univ Sch Med, Dept Surg, Transplant Div, Indianapolis, IN 46202 USA
基金
美国国家卫生研究院;
关键词
VON-WILLEBRAND-FACTOR; HUMAN XENOREACTIVE ANTIBODIES; MESENCHYMAL STROMAL CELLS; N-GLYCOLYLNEURAMINIC ACID; ENDOTHELIAL-CELLS; HUMAN PLATELETS; IN-VITRO; HEPATIC XENOTRANSPLANTATION; CONSUMPTIVE COAGULOPATHY; PORCINE CYTOMEGALOVIRUS;
D O I
10.1097/TP.0000000000001319
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Experience with clinical liver xenotransplantation has largely involved the transplantation of livers from nonhuman primates. Experience with pig livers has been scarce. This brief review will be restricted to assessing the potential therapeutic impact of pig liver xenotransplantation in acute liver failure and the remaining barriers that currently do not justify clinical trials. A relatively new surgical technique of heterotopic pig liver xenotransplantation is described that might play a role in bridging a patient with acute liver failure until either the native liver recovers or a suitable liver allograft is obtained. Other topics discussed include the possible mechanisms for the development of the thrombocytopenis that rapidly occurs after pig liver xenotransplantation in a primate, the impact of pig complement on graft injury, the potential infectious risks, and potential physiologic incompatibilities between pig and human. There is cautious optimism that all of these problems can be overcome by judicious genetic manipulation of the pig. If liver graft survival could be achieved in the absence of thrombocytopenia or rejection for a period of even a few days, there may be a role for pig liver transplantation as a bridge to allotransplantation in carefully selected patients.
引用
收藏
页码:2039 / 2047
页数:9
相关论文
共 99 条
[1]  
BADIMON L, 1987, J LAB CLIN MED, V110, P634
[2]   Absence of humoral and cellular alloreactivity in baboons sensitized to pig antigens [J].
Baertschiger, RM ;
Dor, FJMF ;
Prabharasuth, D ;
Kuwaki, K ;
Cooper, DKC .
XENOTRANSPLANTATION, 2004, 11 (01) :27-32
[3]   Characterization of human xenoreactive antibodies in liver failure patients exposed to pig hepatocytes after bioartificial liver treatment - An ex vivo model of pig to human xenotransplantation [J].
Baquerizo, A ;
Mhoyan, A ;
Kearns-Jonker, A ;
Arnaout, WS ;
Shackleton, C ;
Busuttil, RW ;
Demetriou, AA ;
Cramer, DV .
TRANSPLANTATION, 1999, 67 (01) :5-18
[4]   Porcine Extrahepatic Vascular Endothelial Asialoglycoprotein Receptor 1 Mediates Xenogeneic Platelet Phagocytosis In Vitro and in Human-to-Pig Ex Vivo Xenoperfusion [J].
Bongoni, Anjan K. ;
Kiermeir, David ;
Denoyelle, Julie ;
Jenni, Hansjoerg ;
Burlak, Christopher ;
Seebach, Joerg D. ;
Voegelin, Esther ;
Constantinescu, Mihai A. ;
Rieben, Robert .
TRANSPLANTATION, 2015, 99 (04) :693-701
[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]   In vivo regulation of von Willebrand factor synthesis -: von Willebrand factor production in endothelial cells after lung transplantation between normal pigs and von Willebrand factor-deficient pigs [J].
Brouland, JP ;
Egan, T ;
Roussi, J ;
Bonneau, M ;
Pignaud, G ;
Bal, C ;
Vaiman, M ;
André, P ;
Hervé, P ;
Mazmanian, GM ;
Drouet, L .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1999, 19 (12) :3055-3062
[7]   The fate of human platelets perfused through the pig liver: implications for xenotransplantation [J].
Burlak, Christopher ;
Paris, Leela L. ;
Chihara, Ray K. ;
Sidner, Richard A. ;
Reyes, Luz M. ;
Downey, Susan M. ;
Tector, A. Joseph .
XENOTRANSPLANTATION, 2010, 17 (05) :350-361
[8]   Silencing Porcine CMAH and GGTA1 Genes Significantly Reduces Xenogeneic Consumption of Human Platelets by Porcine Livers [J].
Butler, James Russell ;
Paris, Leela L. ;
Blankenship, Ross L. ;
Sidner, Richard A. ;
Martens, Gregory R. ;
Ladowski, Joseph M. ;
Li, Ping ;
Estrada, Jose L. ;
Tector, Matthew ;
Tector, A. Joseph .
TRANSPLANTATION, 2016, 100 (03) :571-576
[9]  
CALNE RY, 1968, LANCET, V1, P1176
[10]  
CALNE RY, 1970, LANCET, V1, P103