Update: cardiac xenotransplantation

被引:4
作者
Ekser, Burcin [1 ,2 ]
Cooper, David K. C. [1 ]
机构
[1] Univ Pittsburgh, Med Ctr, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15261 USA
[2] Univ Padua, Kidney & Pancreas Transplantat Unit, Dept Surg & Organ Transplantat, Padua, Italy
关键词
alpha 1,3-galactosyltransferase gene-knockout; cardiac; heart; xenotransplantation;
D O I
10.1097/MOT.0b013e32830fdf89
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Purpose of review To review the latest development in cardiac xenotransplantation in small and large animal models and related in-vitro studies. Recent findings With the recent introduction of a 1,3-galactosyltransferase gene-knockout (GT-KO) pig organs for xenotransplantation, improved cardiac graft survival has been obtained. However, this experience has demonstrated the importance of pig antigens other than Gal alpha 1,3Gal (Gal) antigens (so-called nonGal antigens) as targets for primate anti-pig antibodies. Several in-vitro studies have confirmed that, although the incidence and levels of anti-nonGal antibodies in nonhuman primates and humans are significantly less when compared with total anti-pig antibodies (i.e., anti-Gal + anti-nonGal), they can result in complement-mediated lysis of GT-KO pig cells. More recently, it has been demonstrated that regulatory T cells suppress the cellular xenogeneic response, thus potentially preventing or reducing T-cell-mediated rejection. The importance of thrombotic microarogiopathy as a feature of the immune/inflammatory response and incompatibilities between the coagulation -anticoagulation systems of pig and primate are receiving increasing attention. Development of GT-KO pigs transgenic for one or more 'antithrombotic' genes, for example, CD39 or tissue factor pathway inhibitor, may contribute to overcoming these problems. Summary Although GT-KO pigs have provided an advance over wild-type pigs as a source of organs for transplantation into primates, further genetic modification of GT-KO pigs is required to overcome the remaining immune barriers before a clinical trial of cardiac xenotransplantation can be contemplated.
引用
收藏
页码:531 / 535
页数:5
相关论文
共 48 条
[1]   Soluble Galα(1,3)Gal conjugate combined with hDAF preserves morphology and improves function of cardiac xenografts [J].
Brandl, Ulrike ;
Erhardt, Matthias ;
Michel, Sebastian ;
Joeckle, Hannah ;
Burdorf, Lars ;
Bittmann, Iris ;
Roessle, Matthias ;
Mordstein, Volker ;
Brenner, Paolo ;
Hammer, Claus ;
Reichart, Bruno ;
Schmoeckel, Michael .
XENOTRANSPLANTATION, 2007, 14 (04) :323-332
[2]  
Bühler L, 2000, TRANSPLANTATION, V69, P2296
[3]   Increased immunosuppression, not anticoagulation, extends cardiac xenograft survival [J].
Byrne, Guerard W. ;
Davies, William R. ;
Oi, Keiji ;
Rao, Vinay P. ;
Teotia, Sumeet S. ;
Ricci, David ;
Tazelaar, Henry D. ;
Walker, Randall C. ;
Logan, John S. ;
McGregor, Christopher G. A. .
TRANSPLANTATION, 2006, 82 (12) :1787-1791
[4]   Oxidative stress implication in a new ex-vivo cardiac concordant xenotransplantation model [J].
Charniot, Jean-Christophe ;
Bonnefont-Rousselot, Dominique ;
Albertini, Jean-Paul ;
Zerhouni, Khaled ;
Dever, Sylvie ;
Richard, Isabelle ;
Nataf, Patrick ;
Pavie, Alain ;
Monsuez, Jean-Jacques ;
Delattre, Jacques ;
Artigou, Jean-Yves .
FREE RADICAL RESEARCH, 2007, 41 (08) :911-918
[5]   Inhibition of tissue factor-dependent and -independent coagulation by cell surface expression of novel anticoagulant fusion proteins [J].
Chen, DX ;
Riesbeck, K ;
Kemball-Cook, G ;
McVey, JH ;
Tuddenham, EGD ;
Lechler, RI ;
Dorling, A .
TRANSPLANTATION, 1999, 67 (03) :467-474
[6]   Complete inhibition of acute humoral rejection using regulated expression of membrane-tethered anticoagulants on xenograft endothelium [J].
Chen, DX ;
Weber, M ;
McVey, JH ;
Kemball-Cook, G ;
Tuddenham, EGD ;
Lechler, RI ;
Dorling, A .
AMERICAN JOURNAL OF TRANSPLANTATION, 2004, 4 (12) :1958-1963
[7]   Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys [J].
Chen, G ;
Qian, H ;
Starz, T ;
Sun, HT ;
Garcia, B ;
Wang, XM ;
Wise, Y ;
Liu, YQ ;
Xiang, Y ;
Copeman, L ;
Liu, WH ;
Jevnikar, A ;
Wall, W ;
Cooper, DKC ;
Murase, N ;
Dai, YF ;
Wang, WY ;
Xiong, YL ;
White, DJ ;
Zhong, R .
NATURE MEDICINE, 2005, 11 (12) :1295-1298
[8]   Recent advances in pig-to-human organ and cell transplantation [J].
Cooper, David K. C. ;
Ezzelarab, Mohamed ;
Hara, Hidetaka ;
Ayares, David .
EXPERT OPINION ON BIOLOGICAL THERAPY, 2008, 8 (01) :1-4
[9]   α 1,3-galactosyltransferase gene-knockout pigs for xenotransplantation:: Where do we go from here? [J].
Cooper, David K. C. ;
Dorling, Anthony ;
Pierson, Richard N., III ;
Rees, Michael ;
Seebach, Jorg ;
Yazer, Mark ;
Ohdan, Hideki ;
Awwad, Michel ;
Ayares, David .
TRANSPLANTATION, 2007, 84 (01) :1-7
[10]   Report of the Xenotransplantation Advisory Committee of the International Society for Heart and Lung Transplantation: The present status of xenotransplantation and its potential role in the treatment of end-stage cardiac and pulmonary diseases [J].
Cooper, DKC ;
Keogh, AM ;
Brink, J ;
Corris, PA ;
Klepetko, W ;
Pierson, RN ;
Schmoeckel, M ;
Shirakura, R ;
Stevenson, LW .
JOURNAL OF HEART AND LUNG TRANSPLANTATION, 2000, 19 (12) :1125-1165