Información del artículo
Resumen
No cabe duda de que poder disponer de órganos animales para trasplante solucionaría el problema de su escasez. Para que los xenotrasplantes puedan llegar a ser una realidad clínica, se debe superar de forma consistente tres barreras: la inmunológica, la fisiológica y el riesgo de xenozoonosis. Desde el punto de vista inmunológico, la condición necesaria sería que el xenorrechazo pudiera modularse y transformarse a un allorejection-type. Los avances en la tecnología transgénica han resuelto por completo el rechazo hiperagudo, y así en los ensayos preclínicos de órganos porcinos transgénicos para proteínas reguladoras de complemento realizados hasta el momento se han obtenido sobrevidas máximas de meses para el riñón y el corazón, y de 8 días para el hígado. Estas sobrevidas han permitido estudiar la compatibilidad fisiológica de estos órganos porcinos trasplantados en los monos durante estos períodos.
En cuanto a las barreras infecciosas, con el desarrollo biotecnológico actual en el área de la producción porcina, se asegura el nacimiento de lechones completamente libres de patógenos específicos. En 1997 se demostró in vitro que retrovirus endógenos porcinos podían transfectar linfocitos humanos. Sin embargo, diversos trabajos clínicos, con tejidos u órganos perfundidos confirman la ausencia de infectividad in vivo de estos pacientes por retrovirus porcinos.
Hasta la fecha no se ha comunicado ningún xenotrasplante clínico con órganos porcinos transgénicos. La razón de ello es que existe unanimidad en que todavía las barreras inmunológicas no se han superado. En la actualidad todos los esfuerzos están orientados a estudiar los mecanismos del rechazo vascular agudo retardado para así poder diseñar estrategias que lo prevengan con efectividad.
Palabras clave:
Xenotrasplante
Xenorrechazo
Órganos transgénicos
Xenozoonosis
Supervivencia
h-DAF
The availability of animal organs for transplantation would undoubtedly solve the problem of organ scarcity. For xenotransplantations to become a clinical reality, three barriers must consistently be overcome: immunological and physiological obstacles and the risk of xenozoonosis. From the immunological point of view, the necessary condition would be that xenorejection could be adapted and transformed to the “allorejection-type”. Advances in transgenic technology have completely resolved the problem of hyperacute rejection; thus, in the preclinical trials of transgenic pig organs for complement regulatory proteins performed to date, maximum survivals of months for kidney and heart and of eight days for liver have been obtained. These survivals have enabled the physiological compatibility of these pig-to-monkey transplanted organs to be studied in these time periods.
Concerning infectious obstacles, current biotechnological development in the area of pig production guarantees the birth of piglets completely free of specific pathogens. In 1997 porcine endogenous retroviruses were demonstrated to be able to transfect human lymphocytes in vitro. However, several clinical studies, with perfused tissues or organs confirmed that these patients could not be infected in vivo by porcine retroviruses.
To date, there have been no reports of clinical xenotransplantation with transgenic pig organs because there is unanimous agreement that the immunological barriers remain to be overcome. Currently, all efforts are directed towards studying the mechanisms of acute delayed vascular rejection in order to design effective strategies for its prevention.
Key words:
Xenotransplantation
Xenorejection
Transgenic organs
Xenozoonosis
Survival
hDAF
El Texto completo está disponible en PDF
Bibliografía
[1.]
D. Grant, M. Mendicino, G. Levy.
Xenotransplantation: Just around the corner?.
Surgery, 129 (2001), pp. 243-247
[2.]
M. Jaboulay.
Kidney grafts in the antecubital fossa by arterial and venous anastomosis.
Lyon Med, 107 (1906), pp. 575-592
[3.]
A. Carrel.
The operative technique for vascular anastomoses and transplantation of viscera.
Lyon Med, 98 (1902), pp. 859-873
[4.]
K. Reemtsma, B.H. McCracken, J.V. Schiegel, M. Pearl.
Heterotransplantation of the kidney: two clinical experiences.
Science, 143 (1964), pp. 700-702
[5.]
P.B. Medawar.
The behavior and fate of skin autografts and skin homografs in rabbits.
J Anat, 78 (1944), pp. 176-199
[6.]
R.Y. Calne.
Organ transplantation between widely disparate species.
Trans Proc, 2 (1970), pp. 550-554
[7.]
P. Ramírez, R. Chávez, M. Majado, V. Munitiz, Q. Hernández, M. Loba, et al.
Study of xenograf rejection in a model of liver xenotransplantation from unmodified pig to primate.
Transplant Proc, 31 (1999), pp. 2814-2817
[8.]
UNOS. Disponible en; www.unos.org.
[9.]
R. Matesnz, B. Miranda.
Need for liver transplantation.
Lancet, 28 (1995), pp. 1168-1169
[10.]
ONT. Disponible en; www.Msc.es/ont/esp/home.htm.
[11.]
D.J. White, N. Yannoutsos.
Production of pigs transgenic for human DAF to overcome complement-mediated hyperacute xenograft rejection in man.
Res Immunol, 147 (1996), pp. 88-94
[12.]
J.L. Platt.
New directions for organ transplantation.
Nature, 392 (1998), pp. 11-17
[13.]
A. Dorling, K. Riesbeck, A. Warrens, R. Lechler.
Clinical xenotransplantation of solid organs.
Lancet, 349 (1997), pp. 867-871
[15.]
M.J. Majado, Q. Hernández, P. Ramírez, M. Loba, V. Munitiz, R. Chávez, et al.
Selection criteria of donors and recipients in pig to baboon orthotopic liver xenotransplantation.
Transplant Proc, 31 (1999), pp. 2810-2811
[16.]
A. Muñoz, G. Ramis, F.J. Pallares, J.S. Martínez, R. Chávez, V. Munitiz, et al.
Selection criteria for mothers of future donor candidates for xenotransplantation (pigs to baboon.
Transplant Proc, 31 (1999), pp. 2807-2809
[17.]
Z. Zhang, E. Bedard, Y. Luo, H. Wang, S. Deng, D. Kelvin, et al.
Animal models in xenotransplantation.
Expert Opin Investing Drugs, 9 (2000), pp. 2051-2068
[18.]
E.C. Halperin.
Non human to human organ transplantation: its biologic basis and a potential role for radiation therapy.
Int J Cancer, 96 (2001), pp. 76-89
[19.]
J. Yelamos, P. Ramírez, P. Parrilla.
Animales modificados genéticamente como donantes de órganos en xenotrasplante.
Med Clin, 114 (2000), pp. 342-348
[20.]
J. Yélamos, N. Klix, B. Goyenechea, F. Lozano, Y.L. Chui, A. González-Fernández, et al.
Targeting of non. Ig sequences in place of the V segment by somatic hypermutation.
Nature, 376 (1995), pp. 225-229
[21.]
P.J. Cowan, A. Aminian, H. Barlow, A.A. Brown, C.G. Chen, N. Fisicaro, et al.
Renal xenografts from triple transgenic pigs are not hyperacutely rejected but cause coagulopathy in non immunosuppressed baboons.
Transplantation, 69 (2000), pp. 2504-2515
[22.]
B. Vangerow, J.M. Hecker, R. Lorenz, M. Loss, M. Przemeck, R. Appiah, et al.
C1-inhibitor for treatment of acute vascular xenograft rejection in cynomolgus recipients of h-DAF transgenic porcine kidneys.
Xenotransplantation, 8 (2001), pp. 266-272
[23.]
A. Zaidi, M. Schmoeckel, F. Bhatti, P. Waterworth, M. Tolan, E. Cozzi, et al.
Life supporting pig to primate renal xenotransplantation using genetically modified donors.
Transplantation, 65 (1998), pp. 1584-1590
[24.]
M. Schmoeckel, F.N. Bhatti, A. Zaidi, E. Cozzi, P.D. Waterworth, M.J. Tolan, et al.
Orthotopic heart transplantation in a transgenic pig-toprimate model.
Transplantation, 65 (1998), pp. 1570-1577
[25.]
P. Ramírez, R. Chávez, M. Majado, V. Munitiz, A. Muñoz, O. Hernández, et al.
Life-supporting human complement regulator decay acceleratin factor transgenic pig liver xenograf maintains the metabolic function and coagulation in the nonhuman primate for up to 8 days.
Transplantation, 70 (2000), pp. 989-998
[26.]
J.M. Hecker, R. Lorenz, R. Appiah, B. Vangerow, M. Loss, R. Kunz, et al.
C1 inhibitor for prophylaxis of xenograft rejection after pig to cynomolgus monkey kidney transplantation.
Transplantation, 73 (2002), pp. 688-694
[27.]
C.T. Salerno, D.M. Kulick, C.G. Yeh, M. Guzman Paz, P.J. Higgins, B.A. Benson, et al.
A soluble chimeric inhibitor of C3 and C5 convertases, complement activation blocker-2, prolongs graft survival in pig to rhesus monkey heart transplantation.
Xenotransplantation, 9 (2002), pp. 125-134
[28.]
G. Chen, X.M. Wang, Q.Y. Sun, S.Q. Shen, H. Guo, H. Wang, et al.
Prevention of hyperacute rejection of pig to monkey cardiac xenografts by chinese cobra venom factor.
Transplant Proc, 33 (2001), pp. 3857-3858
[29.]
T. Kozlowski, A. Shimizu, D. Lambrigts, K. Yamada, Y. Fuchimoto, R. Glaser, et al.
Porcine kidney and heart transplantation in baboons undergoing a tolerance induction regimen and antibody adsorption.
Transplantation, 67 (1999), pp. 18-30
[30.]
M. Rodríguez-Gago, A. De Heredia, P. Ramírez, P. Parrilla, P. Aparicio, J. Yélamos.
Human anti-porcine gammadelta T cells xenoreactivity is inhibited by human Fas L expression on porcine endothelial cells.
Transplantation, 72 (2001), pp. 503-509
[31.]
M. Loss, J. Schmidtko, M. Przemeck, R. Kunz, H. Arends, A. Jalali, et al.
A primate model for disscordant pig to primate kidney xenotransplantation without hyperacute graft rejection.
Invest Surg, 14 (2001), pp. 21-29
[32.]
E. Cozzi, F. Bhatti, M. Schmoeckel, G. Chávez, K.G. Smith, A. Zaidi, et al.
Long-term survival of nonhuman primates receiving life-supporting transgenic porcine kidney xenografts.
Transplantation, 70 (2000), pp. 15-21
[34.]
A. Muñoz, F.J. Pallares, G. Ramis, J.S. Martínez, V. Munítiz, P. Ramírez, et al.
Surgical procedure for specific pathogen free piglet production by modified terminal hysterectomy.
Transplant Proc, 31 (1999), pp. 2627-2628
[35.]
R. Matesanz, B. Miranda.
Recomendaciones del Comité Nacional de Xenotrasplante.
[36.]
C. Patience, Y. Takeuchi, R.A. Weiss.
Zoonosis in xenotransplantation.
Curr Oppin Inmunol, 10 (1998), pp. 539-542
[37.]
K. Paridis, G. Langford, Z. Long, W. Heneine, P. Sandstrom, W.M. Switzer, et al.
Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue.
Science, 285 (1999), pp. 1236
[38.]
L.J. Van der Laan, C. Lockey, B.C. Griffeth, F.S. Frasier, C.A. Wilson, et al.
Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice.
Nature, 27 (2000), pp. 29-30
[39.]
W.M. Switzer, R.E. Michler, V. Shanmugam, A. Matthews, A.I. Hussain, A. Wright, et al.
Lack of cross-species transmission of porcine endogenous retrovirus infection to nonhuman primate recipients of porcine cells, tissues, or organs.
Transplantation, 71 (2001), pp. 959-965
[40.]
W.W. Hancock.
The past, present, and future of renal xenotransplantation.
Kidney Int, 51 (1997), pp. 932-944
[41.]
K. Reemtsma.
Renal heterotransplantation from non human primates to man.
Ann NY Acad Sci, 162 (1969), pp. 412-418
[42.]
M. Schmoeckel, F.N.K. Bhatti, A. Zaidi, E. Cozzi, G. Chávez, J. Wallwork, et al.
Splenectomy improves survival of h-DAF transgenic pig kidneys in primates.
Transplant Proc, 31 (1999), pp. 961
[43.]
F.N. Bhatti, A. Zaidi, M. Schmoeckel, E. Cozzi, G. Chávez, J Wallwork, et al.
Survival of life supporting h-DAF transgenic kidneys in primates is enhanced by splenectomy.
Transplant Proc, 30 (1998), pp. 2467
[44.]
B. Soin, K.G. Smith, A. Zaidi, E. Cozzi, J.R. Bradley, D.J. Ostlie, et al.
Physiological aspects of pig to primate renal xenotransplantation.
Kidney Int, 60 (2001), pp. 1592-1597
[45.]
A.J. Cohen, T.S. Larson, P. Dean, J. Logan, L. Diamond, C.G. McGregor, et al.
Renal physiology in pig to baboon xenografts.
Transplant Proc, 33 (2001), pp. 727-728
[46.]
M. Loss, B. Vangerow, J. Schmidtko, R. Kunz, A. Jalali, H. Arends, et al.
Acute vascular rejection is associated with systemic complement activation in a pig to primate kidney xenograft model.
Xenotransplantation, 7 (2000), pp. 186-196
[47.]
M. Loss, M. Przemeck, J. Schmidtko, H. Arends, R. Kunz, K Jager, et al.
Long term survival of cynomolgus monkeys following pig to primate kidney xenotransplantation using h-DAF transgenic donor organs.
Transplant Proc, 32 (2000), pp. 1095-1096
[48.]
A. Zaidi, F. Bhatti, M. Schmoeckel, E. Cozzi, G. Chávez, J. Wallwork, et al.
Kidneys from h-DAF transgenic pigs are physiologically compatible with primates.
Transplant Proc, 30 (1998), pp. 2465-2466
[49.]
J.H. Artrip, P. Kwiatkowski, R.E. Michler, S. Itescu.
Immunologic barriers in pig to primate cardiac xenotransplantation.
Ann Transplant, 2 (1997), pp. 5-11
[50.]
O.P. Minanov, J.H. Artrip, M. Szabolcs, P.A. Kwiatkowski, U. Galili, S. Itescu, et al.
Triple immunosuppression reduces mononuclear cell infiltration and prolongs graft life in pig to newborn baboon cardiac xenotransplantation.
J Thorac Cardiovasc Surg, 115 (1998), pp. 998-1006
[51.]
R.J. Kaplon, R.E. Michler, H. Xu, P.A. Kwiatkowski, N.M. Edwards, J.L. Platt.
Absence of hyperacute rejection in newborn pig to baboon cardiac xenografts.
Transplantation, 59 (1995), pp. 1-6
[52.]
R.J. Kaplon, J.L. Platt, H. Xu, P.A. Kwiatkowski, N.M. Edwards, R.E. Michler.
Prolonged survival of pig cardiac xenografts in unmodified newborn baboons.
Transplant Proc, 26 (1994), pp. 1072
[53.]
N. Fukushima, R. Shirakura, J. Chang, T. Yamaguchi, Y. Kobayashi, M. Yoshitatsu, et al.
Prolonged survival of pig cardiac xenografts in baboons by sequential cardiac transplantation.
Transplant Proc, 30 (1998), pp. 3815-3817
[54.]
L.L. Bailey, S.R. Gundry.
Survival following orthotopic cardiac xenotransplantation between juvenile baboon recipients and concordant and discordant donor species: foundation for clinical trials.
World J Surg, 21 (1997), pp. 943-950
[55.]
P.D. Waterworth, J. Dunning, M. Tolan, E. Cozzi, G. Langford, G. Chávez, et al.
Life supporting pig to baboon heart xenotransplantation.
J Heart Lung Transplant, 17 (1998), pp. 1201-1207
[56.]
D.H. Adams, R.H. Chen, A. Kadner, S. Naficy.
Technique for heterotopic pig heart xenotransplantation in primates.
Ann Thorac Surg, 68 (1999), pp. 265-268
[57.]
R.H. Chen, S. Naficy, J.S. Logan, L.E. Diamond, D.H. Adams.
Hearts from transgenic pigs constructed with CD59/DAF genomic clones demonstrate improved survival in primates.
Xenotransplantation, 6 (1999), pp. 194-200
[58.]
S.S. Lin, B.C. Weidner, G.W. Byrne, L.E. Diamond, J.H. Lawson, C.W. Hoopes, et al.
The role of antibodies in acute vascular rejection ofpig to baboon cardiac transplants.
J Clin Invest, 101 (1998), pp. 1745-1756
[59.]
K.R. McCurry, D.L. Kooyman, C.G. Alvarado, A.H. Cotterell, M.J. Martin, J.S. Logan, et al.
Human complement regulatory proteins protect swine to primate cardiac xenografts from humonal injury.
Nat Med, 1 (1995), pp. 423-427
[60.]
H.J. Schuurman, G. Pino Chávez, M.J. Phillips, L. Thomas, D.J. White, E. Cozzi.
Incidence of hyperacute rejection in pig to primate transplantation using organs from h-DAF transgenic donors.
Transplantation, 73 (2002), pp. 1146-1151
[61.]
J. Goddard, J. Dunning, J. Horsley, C. Atkinson, G. Pino Chávez, J. Wallwork.
Histopathology of cardiac xenograft rejection in the pig to baboon model.
J Heart Lung Transplant, 21 (2002), pp. 474-484
[62.]
K. Miyazaki, S. Watanabe, T. Miyatake, T. Watanabe, S. Kubota, T. Murashita, et al.
Structural analysis of hyperacute rejection in cardiac xenotransplantation: comparison of two different donor recipient species combinations.
Transplant Proc, 32 (2000), pp. 946
[63.]
C.M. Vial, D.J. Ostlie, F.N. Bhatti, E. Cozzi, M. Goddard, G.P. Chávez, et al.
Life supporting function for over one month of a transgenic porcine heart in a baboon.
J Heart Lung Transplant, 19 (2000), pp. 224-229
[64.]
F.N. Bhatti, M. Schmoeckel, A. Zaidi, E. Cozzi, G. Chávez, M. Goddard, et al.
Three month survival of h-DAFF transgenic pig hearts transplanted into primates.
Transplant Proc, 31 (1999), pp. 958
[65.]
M. Przemeck, B. Vangerow, M. Loss, J. Schmidtko, J. Klempnauer, H. Ruckoldt, et al.
Hemodynamic consequences of porcine kidney xenograft reperfusion in cynomolgus monkeys.
Transplantation, 71 (2001), pp. 1512-1514
[66.]
P. Brenner, H. Reichenspurner, M. Schmoeckel, C. Wimmer, A. Rucker, V. Eder, et al.
Prevention of hyperacute xenograft rejection in orthotopic xenotransplantation of pig hearts into baboons using immunoadsorption of antibodies and complement factors.
Transpl Int, 13 (2000), pp. S508-517
[67.]
P. Brenner, M. Schmoeckel, H. Reichenspurner, T. Felbinger, M. Hinz, V. Eder, et al.
Technique of immunoapheresis in heterotopic and orthotopic xenotransplantation of pig hearts into cynomolgus and rhesus monkeys.
Transplant Proc, 32 (2000), pp. 1087-1088
[68.]
R.H. Chen, A. Kadner, D.H. Adams.
Monitoring pig to primate cardiac xenografts with live Internet images of recipients and xenograft telemetric signals: histologic and immunohistochemical correlations.
J Heart Lung Transplant, 19 (2000), pp. 591-597
[69.]
L.L. Bailey, S.L. Nehlsen-Cannarella, W. Concepcion, W.B. Jolle.
Baboon-to-human cardiac xenotansplantation in a neonate.
Jama, 254 (1985), pp. 3321-3329
[70.]
R.Y. Calne, H.J.O. White, B.M. Herbertson, P.R. Millard, D.R. Davis, J.R. Salaman, et al.
Pig to baboon liver xenografts.
Lancet, 1 (1968), pp. 1176-1178
[71.]
R.Y. Calne, D.R. Davis, J.R. Pena, H. Balner, M. De Vries, B.M. Herbertson, et al.
Hepatic allgrafts and xenografts in primates.
Lancet, 1 (1970), pp. 103-106
[72.]
J. Powelson, A.B. Cosimi, W. Asuten Jr, M. Bailen, R. Colvin, P. Gianello, et al.
Porcine to primate orthotopic liver transplantation.
Transplant Proc, 26 (1994), pp. 1353-1354
[73.]
Y. Luo, S. Kosanke, L. Mieles, T. Kobayashi, S.F. Li, M. Niekrasz, et al.
Comparatie histopathology of hepatic allografts and xenografts in the nonhuman primates.
Xenotransplantation, 5 (1998), pp. 197-206
[74.]
L. Makowka, G.D. Wu, A. Hoffman, L. Podesta, L. Sher, P.J. Tuso, et al.
Immunohistopathologic lesions associated with the rejection of a pig to human liver xenograft.
Transplant Proc, 26 (1998), pp. 1074-1075
[76.]
P. Ramírez, R. Chávez, M. Majado, V. Munitiz, A. Muñoz, Q. Hernández, et al.
The porcine liver supports metabolic homeostasis in the nonhuman primate: experimental study in a model of orthotopic liver transplantation from h-DAF transgenic pig to baboon.
Transplant Proc, 32 (2000), pp. 1112-1113
[77.]
V. Munitiz, P. Ramírez, Q. Hernández, M. Loba, R. Chávez, A. Muñoz, et al.
Hematologic and hepatic function profile comparison between pig and baboon in an orthotopic liver xenotransplantation model.
Transplant Proc, 31 (1999), pp. 2641-2642
[78.]
A. Minguela, P. Ramírez, C. Carrascosa, M.J. Majado, V. Munitiz, Q. Hernández, et al.
Identification of porcine proteins in baboon sera after pig liver xenotransplantation.
Transplant Proc, 31 (1999), pp. 2635-2637
[79.]
M.J. Majado, P. Ramírez, A. Minguela, Q. Hernández, C. González, M. Loba, et al.
Evolution of blood coagulation factors and hemotherapeutic support in three pig to baboon orthotopic liver xenotransplants.
Transplant Proc, 31 (1999), pp. 2622-2624
[80.]
M.F. Levy, J. Crippin, S. Sutton, G. Netto, J. McCormack, T. Curiel, et al.
Liver allotransplantation after extracorporeal hepatic support with transgenic (hCD55/hCD59) porcine livers: clinical results and lack of pig-to-human transmission of the porcine endogenous retrovirus.
Transplantation, 69 (2000), pp. 272-280
[81.]
K. Paridis, G. Langford, Z. Long, W. Heneine, P. Sandstrom, W.M. Switzer, et al.
Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. The XEN 111 Study Group.
Science, 285 (1999), pp. 1236-1241
[82.]
Xenotransplantation: time to leave the laboratory [editorial]..
Lancet, 354 (1999), pp. 1657
[83.]
P. Parrilla, P. Ramírez.
Luces y sombras en el trasplante hepático.
Med Clin (Barc), 115 (2000), pp. 542-545
[84.]
P. Ramírez, R. Chávez, M. Majado, V. Munitiz, Q. Hernández, M. Loba, et al.
Study of xenograft rejection in a model of liver xenotransplantament from unmodified pig to primate.
Transplant Proc, 31 (1999), pp. 2814-2817
[85.]
C.L. Lau, W.C. Daggett, M.F. Yeatman, P. Chai, S.S. Lin, A.J. Lodge, et al.
The role of antiboidies in dysfunction of pig to baboon pulmonary transplants.
J Thorac Cardiovasc Surg, 120 (2000), pp. 29-38
[86.]
R.J. Kaplon, J.L. Platt, P.A. Kwiatkowski, N.M. Edwards, H. Xu, A.S. Shah, et al.
Absence of hyperacute rejection in pig to primate orthotopic pulmonary xenografts.
Transplantation, 59 (1995), pp. 410-416
[87.]
P. Macchiarini, R. Oriol, A. Azimzadeh, V. De Montpreville, P. Wolf, P. Dartevelle.
Characterization of a pig to goat orthotopic lung xenotransplantation model to study beyond hyperacute rejection.
J Thorac Cardiovasc Surg, 118 (1999), pp. 805-814
[88.]
F.P. Reinholt, K. Hultenby, A. Tibell, O. Korsgren, C.G. Groth.
Survival of fetal porcine pancreatic islet tisuue transplanted to a diabetic patient: findings by ultraestructural immunocytochemistry.
Xenotransplantation, 5 (1998), pp. 222-225
[89.]
H.B. Stockmann, C.A. Hiemstra, R.L. Marquet, J.N. Ijzermans.
Extracorporeal perfusion for the treatment of acute liver failure.
Ann Surg, 231 (2000), pp. 460-470
[90.]
T.E. Starlz, J. Fung, A. Tzakis, S. Todo, A.J. Demetris, J.R. Marino, et al.
Baboon-to-human liver transplantation.
Lancet, 341 (1993), pp. 65-71
[91.]
B. Samstein, J.L. Platt.
Physiologic immunologic hurdles to xenotransplantation.
Am Soc Nephrol, 12 (2001), pp. 182-193
[92.]
A. Simon, C. Hammer.
Xenotransplantation so close but yet so far.
Transplantation, 73 (2002), pp. 1-2
[93.]
C. Margarit, I. Bilbao, R. Charco, J.L. Lázaro, E. Hidalgo, E. Allende, et al.
Auxiliary heterotopic liver transplantation with portal arterialization for fulminant hepatic faillure.
Liver Transplantation, 6 (2000), pp. 805-809
[94.]
P. Fiorante, Y. Banz, P.J. Mohacsi, A. Kappeler, W.A. Wuillemin, P. Macchiarini, et al.
Low molecular weight dextran sulfate prevents complement activation and delays hyperacute rejection in pig-tohuman xenotransplantation models.
Xenotransplantation, 8 (2001), pp. 24-35
[95.]
J.Z. Appel 3rd, I.P. Alwayn, L. Buhler, H.A. DeAngelis, S.C. Robson, D.K. Cooper.
Modulation of platelet aggregation in baboons: implications for mixed chimerism in xenotransplantation. I. The roles of individual components of a transplantation conditioning regimen and of pig peripheral blood progenitor cells.
Transplantation, 72 (2001), pp. 1299-1305
[96.]
M. Jonker, J.K. Rijkelijkhuizen, K.G. Haanstra, E.M. Kuhn, J. Ringers, E. Bouwman.
T cell directed immunosuppression allows prolonged survival of xenogeneic pig islets in monkeys.
Transplant Proc, 33 (2001), pp. 726
[97.]
M. Basker, L. Buhler, I.P. Alwayn, J.Z. Appel 3rd, D.K. Cooper.
Pharmacotherapeutic agents in xenotransplantation.
Expert Opin Pharmacother, 1 (2000), pp. 757-769
[98.]
M.L. Cayuela, A. Carrillo, P. Ramírez, P. Parrilla, J. Yélamos.
Genomics instability in a PARP-1 cell line expressing PARP-1 DNA binding domains.
Biochem Biophys Res Commun, 285 (2001), pp. 289-294
[99.]
J.I. Rodríguez-Barbosa, Y. Zhao, R. Barth, G. Zhao, J.S. Arn, D.H. Sachs, et al.
Enhanced CD4 reconstitution by grafting neonatal porcine tissue in alternative locations is associated with donor-specific tolerance and suppression of pre-existing xenoreactive antibodies.
Trasnplantation, 72 (2001), pp. 1223-1231
[100.]
Consejo de Europa, Asamblea Parlamentaria. Recomendación sobre xenotrasplante [Documento 8166]. Aprobado el 29 de enero de 1999
Copyright © 2002. Asociación Española de Cirujanos
