Abstract
Facilitation of solid organ and cell transplantation depends on metabolic and immunologic factors that can be manipulated ex vivo and in vivo using gene transfer technology. Vectors have been developed which can optimally transfer relevant genes to various tissues and organs. Interventions aimed at promoting tissue preservation before transplantation, prevention of oxidative stress and immunological rejection have recently become attractive options using viral and nonviral gene delivery vehicles. Further understanding of the mechanisms involved in tolerance induction as well as the facilitation of xenogeneic engraftment have made possible a variety of avenues that can be exploited using gene transfer technology.
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References
Halloran P . Non-immunologic tissue injury and stress in chronic allograft dysfunction Graft 1998 1: 25–29
Knechtle SJ et al. Histocompatibility and liver transplantation Surgery 1993 114: 667–671; discussion 671–672
Pirsch JD et al. Determinants of graft survival after renal transplantation Transplantation 1996 61: 1581–1586
Perico N, Remuzzi G . Prevention of transplant rejection: current treatment guidelines and future developments Drugs 1997 54: 533–570
Sykes M . Immunobiology of transplantation FASEB J 1996 10: 721–730
Alexander DZ et al. Analysis of effector mechanisms in murine cardiac allograft rejection Transpl Immunol 1996 4: 46–48
Jaeschke H . Reactive oxygen and ischemia/reperfusion injury of the liver Chem Biol Interact 1991 79: 115–136
Nagano H, Tilney NL . Chronic allograft failure: the clinical problem Am J Med Sci 1997 313: 305–309
Tilney NL, Kusaka M, Pratschke J, Wilhelm M . Chronic rejection Transplant Proc 1998 30: 1590–1594
Mueller AR et al. The extracellular matrix: an early target of preservation/reperfusion injury and acute rejection after small bowel transplantation Transplantation 1998 65: 770–776
Wyble CW et al. Physiologic concentrations of TNFalpha and IL-1beta released from reperfused human intestine upregulate E-selectin and ICAM-1 J Surg Res 1996 63: 333–338
De Greef KE et al. Neutrophils and acute ischemia–reperfusion injury (in process citation) J Nephrol 1998 11: 110–122
Weight SC, Bell PR, Nicholson ML . Renal ischaemia–reperfusion injury Br J Surg 1996 83: 162–170
Kurokawa T et al. Mechanism and prevention of ischemia–reperfusion injury of the liver Semin Surg Oncol 1996 12: 179–182
Jaeschke H et al. Mechanisms of inflammatory liver injury: adhesion molecules and cytotoxicity of neutrophils Toxicol Appl Pharmacol 1996 139: 213–226
Thornton AJ et al. Cytokine-induced gene expression of a neutrophil chemotactic factor/IL-8 in human hepatocytes J Immunol 1990 144: 2609–2613
Lentsch AB et al. Chemokine involvement in hepatic ischemia/reperfusion injury in mice: roles for macrophage inflammatory protein-2 and Kupffer cells Hepatology 1998 27: 507–512
Lentsch AB et al. Chemokine involvement in hepatic ischemia/reperfusion injury in mice: roles for macrophage inflammatory protein-2 and KC Hepatology 1998 27: 1172–1177
Frangogiannis NG, Youker KA, Entman ML . The role of the neutrophil in myocardial ischemia and reperfusion Exs 1996 76: 263–284
Gibbs P et al. Adhesion molecule expression (ICAM-1, VCAM-1, E-selectin and PECAM) in human kidney allografts Transpl Immunol 1993 1: 109–113
Yamaguchi Y et al. Monocyte chemoattractant protein-1 enhances expression of intercellular adhesion molecule-1 following ischemia–reperfusion of the liver in rats Hepatology 1998 27: 727–734
Andrews FJ, Malcontenti-Wilson C, O’Brien PE . Expression of adhesion molecules and leukocyte recruitment into gastric mucosa following ischemia–reperfusion Dig Dis Sci 1997 42: 326–332
Taylor PM, Rose ML, Yacoub MH, Pigott R . Induction of vascular adhesion molecules during rejection of human cardiac allografts Transplantation 1992 54: 451–457
Colletti LM et al. The role of cytokine networks in the local liver injury following hepatic ischemia/reperfusion in the rat Hepatology 1996 23: 506–514
Essani NA et al. Cytokine-induced upregulation of hepatic intercellular adhesion molecule-1 messenger RNA expression and its role in the pathophysiology of murine endotoxin shock and acute liver failure Hepatology 1995 21: 1632–1639
Essani NA, McGuire GM, Manning AM, Jaeschke H . Differential induction of mRNA for ICAM-1 and selectins in hepatocytes, Kupffer cells and endothelial cells during endotoxemia Biochem Biophys Res Commun 1995 211: 74–82
Schlayer HJ et al. Involvement of tumor necrosis factor in endotoxin-triggered neutrophil adherence to sinusoidal endothelial cells of mouse liver and its modulation in acute phase J Hepatol 1988 7: 239–249
Meldrum DR et al. Adenosine decreases post-ischaemic cardiac TNF-alpha production: anti-inflammatory implications for preconditioning and transplantation Immunology 1997 92: 472–477
Bottino R et al. Transplantation of allogeneic islets of Langerhans in the rat liver: effects of macrophage depletion on graft survival and microenvironment activation Diabetes 1998 47: 316–323
Hancock WH et al. Cytokines, adhesion molecules, and the pathogenesis of chronic rejection of rat renal allografts Transplantation 1993 56: 643–650
Schlayer HJ et al. Enhancement of neutrophil adherence to isolated rat liver sinusoidal endothelial cells by supernatants of lipopolysaccharide-activated monocytes. Role of tumor necrosis factor J Hepatol 1987 5: 311–321
Shirasugi N et al. Up-regulation of oxygen-derived free radicals by interleukin-1 in hepatic ischemia/reperfusion injury Transplantation 1997 64: 1398–1403
Shirasugi N et al. Interleukin-1 receptor blockade attenuates oxygen-derived free radical production and microcirculatory disturbances in ischemia/reperfusion injury in the liver Transplant Proc 1997 29: 371–373
Natori S et al. Prostaglandin E1 protects against ischemia–reperfusion injury of the liver by inhibition of neutrophil adherence to endothelial cells Transplantation 1997 64: 1514–1520
Jaeschke H . Preservation injury: mechanisms, prevention and consequences J Hepatol 1996 25: 774–780
Marubayashi S et al. Protective effect of monoclonal antibodies to adhesion molecules on rat liver ischemia – reperfusion injury Surgery 1997 122: 45–52
Oubenaissa A et al. Evidence for an involvement of the neutrophil integrin lymphocyte function-associated antigen-1 in early failure of heart transplants Circulation 1996 94: II254–259
DeMeester SR et al. Attenuation of rat lung isograft reperfusion injury with a combination of anti-ICAM-1 and anti-beta2 integrin monoclonal antibodies Transplantation 1996 62: 1477–1485
Bulkley GB . Free radical-mediated reperfusion injury: a selective review Br J Cancer Suppl 1987 8: 66–73
Schneeberger H et al. Prevention of acute renal failure after kidney transplantation by treatment with rh-SOD: interim analysis of a double-blind placebo-controlled trial Transplant Proc 1990 22: 2224–2225
Land W et al. The beneficial effect of human recombinant superoxide dismutase on acute and chronic rejection events in recipients of cadaveric renal transplants Transplantation 1994 57: 211–217
Bennett JF, Bry WI, Collins GM, Halasz NA . The effects of oxygen free radicals on the preserved kidney Cryobiology 1987 24: 264–269
Land W, Zweler JL . Prevention of reperfusion-induced, free radical-mediated acute endothelial injury by superoxide dismutase as an effective tool to delay/prevent chronic renal allograft failure: a review Transplant Proc 1997 29: 2567–2568
Lee PH et al. Protective effect of superoxide dismutase and allopurinol on oxygen free radical-induced damage to the kidney Transplant Proc 1992 24: 1353–1354
Mizoe A et al. Preventive effects of superoxide dismutase derivatives modified with monosaccharides on reperfusion injury in rat liver transplantation J Surg Res 1997 73: 160–165
Shiraishi T et al. Free radical-mediated tissue injury in acute lung allograft rejection and the effect of superoxide dismutase Ann Thorac Surg 1997 64: 821–825
Wang P et al. Overexpression of human copper, zinc-superoxide dismutase (SOD1) prevents postischemic injury Proc Natl Acad Sci USA 1998 95: 4556–4560
Woo YJ et al. Recombinant adenovirus-mediated cardiac gene transfer of superoxide dismutase and catalase attenuates postischemic contractile dysfunction Circulation 1998 98: II255–260
Zwacka RM et al. Redox gene therapy for ischemia/reperfusion injury of the liver reduces AP1 and NF-kappaB activation Nature Med 1998 4: 698–704
Jaeschke H . Mechanisms of oxidant stress-induced acute tissue injury (see comments) Proc Soc Exp Biol Med 1995 209: 104–111
Jaeschke H, Bautista AP, Spolarics Z, Spitzer JJ . Superoxide generation by Kupffer cells and priming of neutrophils during reperfusion after hepatic ischemia Free Radic Res Commun 1991 15: 277–284
Benhamou PY et al. Adenovirus-mediated catalase gene transfer reduces oxidant stress in human, porcine and rat pancreatic islets Diabetologia 1998 41: 1093–1100
Pattison JM, Krensky AM . New insights into mechanisms of allograft rejection Am J Med Sci 1997 313: 257–263
Jaeschke H, Smith CW . Mechanisms of neutrophil-induced parenchymal cell injury (see comments) J Leukoc Biol 1997 61: 647–653
Farhood A et al. Intercellular adhesion molecule 1 (ICAM-1) expression and its role in neutrophil-induced ischemia-reperfusion injury in rat liver J Leukoc Biol 1995 57: 368–374
Springer TA . Adhesion receptors of the immune system Nature 1990 346: 425–434
Isobe M, Yagita H, Okumura K, Ihara A . Specific acceptance of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1 Science 1992 255: 1125–1127
Cosimi AB et al. In vivo effects of monoclonal antibody to ICAM-1 (CD54) in nonhuman primates with renal allografts J Immunol 1990 144: 4604–4612
Kato Y et al. Specific acceptance of fetal bowel allograft in mice after combined treatment with anti-intercellular adhesion molecule-1 and leukocyte function-associated antigen-1 antibodies Ann Surg 1996 223: 94–100
Kaplon RJ et al. Short course single agent therapy with an LFA-3-IgG1 fusion protein prolongs primate cardiac allograft survival Transplantation 1996 61: 356–363
Sultan P et al. Blockade of CD2-LFA-3 interactions protects human skin allografts in immunodeficient mouse/human chimeras Nat Biotechnol 1997 15: 759–762
Gojo S et al. Gene transfer into the donor heart during cold preservation for heart transplantation Ann Thorac Surg 1998 65: 647–652
Drazan KE et al. Adenovirus-mediated gene transfer in the transplant setting. Part III. Variables affecting gene transfer in liver grafts Transplantation 1995 59: 670–673
Shaked A et al. Adenovirus-mediated gene transfer in the transplant setting. II. Successful expression of transferred cDNA in syngeneic liver grafts Transplantation 1994 57: 1508–1511
Csete ME et al. Adenovirus-mediated gene transfer in the transplant setting. I. Conditions for expression of transferred genes in cold-preserved hepatocytes Transplantation 1994 57: 1502–1507
Fanslow WC et al. Regulation of alloreactivity in vivo by a soluble form of the interleukin-1 receptor Science 1990 248: 739–742.
Shiraishi M et al. The inhibitor cytokine interleukin-1 receptor antagonist synergistically augments cyclosporine immunosuppression in a rat cardiac allograft model J Surg Res 1995 58: 465–470
Dana MR, Yamada J, Streilein JW . Topical interleukin 1 receptor antagonist promotes corneal transplant survival Transplantation 1997 63: 1501–1507
Batten P, Yacoub MH, Rose ML . Effect of human cytokines (IFN-gamma, TNF-alpha, IL-1 beta, IL-4) on porcine endothelial cells: induction of MHC and adhesion molecules and functional significance of these changes Immunology 1996 87: 127–133
Bergese et al. Regulation of endothelial VCAM-1 expression in murine cardiac grafts. Roles for TNF and IL4 Am J Pathol 1995 146: 989–998
Qin L et al. Retrovirus-mediated transfer of viral IL-10 gene prolongs murine cardiac allograft survival J Immunol 1996 156: 2316–2323
Qin L et al. Multiple vectors effectively achieve gene transfer in a murine cardiac transplantation model. Immunosuppression with TGF-beta 1 or vIL-10 Transplantation 1995 59: 809–816
Qin L et al. Adenovirus-mediated gene transfer of viral interleukin-10 inhibits the immune response to both alloantigen and adenoviral antigen Hum Gene Ther 1997 8: 1365–1374
Drazan KE et al. Transduction of hepatic allografts achieves local levels of viral IL-10 which suppress alloreactivity in vitro J Surg Res 1995 59: 219–223
Drazan KE et al. Adenovirus-mediated gene transfer in the transplant setting: early events after orthotopic transplantation of liver allografts expressing TGF-betal Transplantation 1996 62: 1080–1084
He XY et al. Treatment with interleukin-4 prolongs allogeneic neonatal heart graft survival by inducing T helper 2 responses Transplantation 1998 65: 1145–1152
Takeuchi T et al. Murine interleukin 4 transgenic heart allograft survival prolonged with down-regulation of the Th1 cytokine mRNA in grafts Transplantation 1997 64: 152–157
Rabinovitch A et al. Combined therapy with interleukin-4 and interleukin-10 inhibits autoimmune diabetes recurrence in syngeneic islet-transplanted nonobese diabetic mice. Analysis of cytokine mRNA expression in the graft Transplantation 1995 60: 368–374
Smith DK et al. Interleukin-4 or interleukin-10 expressed from adenovirus-transduced syngeneic islet grafts fails to prevent beta cell destruction in diabetic NOD mice Transplantation 1997 64: 1040–1049
Hawley RG, Lieu FH, Fong AZ, Hawley TS . Versatile retroviral vectors for potential use in gene therapy Gene Therapy 1994 1: 136–138
Wiznerowicz M, Fong AZ, Mackiewicz A, Hawley RG . Double-copy bicistronic retroviral vector platform for gene therapy and tissue engineering: application to melanoma vaccine development Gene Therapy 1997 4: 1061–1068
Madsen JC, Superina RA, Wood KJ, Morris PJ . Immunological unresponsiveness induced by recipient cells transfected with donor MHC genes Nature 1988 332: 161–164
Sachs DH et al. Induction of specific tolerance to MHC-disparate allografts through genetic engineering Exp Nephrol 1993 1: 128–133
Madsen JC et al. Transplantation tolerance prevents cardiac allograft vasculopathy in major histocompatibility complex class I-disparate miniature swine Transplantation 1998 65: 304–313
Knechtle SJ et al. Induction of specific tolerance by intrathymic injection of recipient muscle cells transfected with donor class I major histocompatibility complex (see comments) Transplantation 1994 57: 990–996
Knechtle SJ et al. Direct MHC class I complementary DNA transfer to thymus induces donor-specific unresponsiveness, which involves multiple immunologic mechanisms J Immunol 1997 159: 152–158
Larsen CP, Pearson TC . The CD40 pathway in allograft rejection, acceptance, and tolerance Curr Opin Immunol 1997 9: 641–647
Sempowski GD, Rozenblit J, Smith T, Phipps RP . Human orbital fibroblasts are activated through CD40 to induce proinflammatory cytokine production Am J Physiol 1998 274: C707–714
Dechanet J et al. CD40 ligand stimulates proinflammatory cytokine production by human endothelial cells J Immunol 1997 159: 5640–5647
Mach F et al. Functional CD40 ligand is expressed on human vascular endothelial cells, smooth muscle cells, and macrophages: implications for CD40–CD40 ligand signaling in atherosclerosis Proc Natl Acad Sci USA 1997 94: 1931–1936
Kiener PA et al. Stimulation of CD40 with purified soluble gp39 induces proinflammatory responses in human monocytes J Immunol 1995 155: 4917–4925
Henn V et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells Nature 1998 391: 591–594
Karmann et al. CD40 on human endothelial cells: inducibility by cytokines and functional regulation of adhesion molecule expression Proc Natl Acad Sci USA 1995 92: 4342–4346
Yellin MJ et al. Functional interactions of T cells with endothelial cells: the role of CD40L–CD40-mediated signals J Exp Med 1995 182: 1857–1864
Akifusa S et al. Increase in Bcl-2 level promoted by CD40 ligation correlates with inhibition of B cell apoptosis induced by vacuolar type H(+)-ATPase inhibitor Exp Cell Res 1998 238: 82–89
Schauer SL, Bellas RE, Sonenshein GE . Dominant signals leading to inhibitor kappaB protein degradation mediate CD40 ligand rescue of WEHI 231 immature B cells from receptor-mediated apoptosis J Immunol 1998 160: 4398–4405
Sartori A et al. Interleukin-12: an immunoregulatory cytokine produced by B cells and antigen-presenting cells Methods 1997 11: 116–127
Peng X et al. IL-12 up-regulates CD40 ligand (CD154) expression on human T cells J Immunol 1998 160: 1166–1172
Van Gool SW, Vandenberghe P, de Boer M, Ceuppens JL . CD80, CD86 and CD40 provide accessory signals in a multiple-step T-cell activation model Immunol Rev 1996 153: 47–83
Lenschow DJ, Walunas TL, Bluestone JA . CD28/B7 system of T cell costimulation Annu Rev Immunol 1996 14: 233–258
Schweitzer AN, Sharpe AH . The complexity of the B7-CD28/CTLA-4 costimulatory pathway Agents Actions Suppl 1998 49: 33–43
Rossini AA et al. Induction of immunological tolerance to islet allografts Cell Transplant 1996 5: 49–52
Parker DC et al. Survival of mouse pancreatic islet allografts in recipients treated with allogeneic small lymphocytes and antibody to CD40 ligand Proc Natl Acad Sci USA 1995 92: 9560–9564
Larsen CP et al. CD40-gp39 interactions play a critical role during allograft rejection. Suppression of allograft rejection by blockade of the CD40–gp39 pathway Transplantation 1996 61: 4–9
Kirk AD et al. CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates Proc Natl Acad Sci USA 1997 94: 8789–8794
Larsen CP et al. Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways Nature 1996 381: 434–438
Elwood ET et al. Prolonged acceptance of concordant and discordant xenografts with combined CD40 and CD28 pathway blockade Transplantation 1998 65: 1422–1428
Lenschow DJ et al. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4Ig Science 1992 257: 789–792
Yi-qun Z, Lorre K, de Boer M, Ceuppens JL . B7-blocking agents, alone or in combination with cyclosporin A, induce antigen-specific anergy of human memory T cells J Immunol 1997 158: 4734–4740
Chahine AA et al. Local CTLA4Ig synergizes with one-dose anti-LFA-1 to achieve long-term acceptance of pancreatic islet allografts Transplant Proc 1994 26: 3296
Bluestone JA . Costimulation and its role in organ transplantation Clin Transplant 1996 10: 104–109
Chahine AA, Stoeckert C, Lau HT . Local immunomodulation to promote co-stimulatory blockade Clin Transplant 1995 9: 215–218
Steurer W et al. Ex vivo coating of islet cell allografts with murine CTLA4/Fc promotes graft tolerance J Immunol 1995 155: 1165–1174
Lenschow DJ et al. Inhibition of transplant rejection following treatment with anti-B7-2 and anti-B7-1 antibodies Transplantation 1995 60: 1171–1178
Levisetti MG et al. Immunosuppressive effects of human CTLA4Ig in a non-human primate model of allogeneic pancreatic islet transplantation J Immunol 1997 159: 5187–5191
Chahine AA et al. Immunomodulation of pancreatic islet allografts in mice with CTLA4Ig secreting muscle cells Transplantation 1995 59: 1313–1318
Gainer AL et al. Expression of CTLA4-Ig by biolistically transfected mouse islets promotes islet allograft survival Transplantation 1997 63: 1017–1021
Olthoff KM et al. Adenovirus-mediated gene transfer into cold-preserved liver allografts: survival pattern and unresponsiveness following transduction with CTLA4Ig Nature Med 1998 4: 194–200
Kita Y et al. Prolonged rat cardiac allograft survival using adenoviral vector containing the CTLA4Ig gene Transplant Proc 1998 30: 1079–1080
Gainer AL et al. Prolongation of allograft survival of transfected islets expressing human CTLA4-Ig, human soluble Fas ligand or a combination of the two Transplant Proc 1998 30: 534
Banchereau J, Steinman RM . Dendritic cells and the control of immunity Nature 1998 392: 245–252
Steptoe RJ, Thomson AW . Dendritic cells and tolerance induction Clin Exp Immunol 1996 105: 397–402
Lu L, Khoury S, Sayegh M, Thomson AW . Dendritic cell tolerogenicity and prospects for therapy of allograft rejection and autoimmune disease. In: Lotze MT, Thomson AW (eds). Dendritic cells: Biology and Clinical Applications Academic Press: San Diego 1998 (in press
Lu L et al. Adenoviral delivery of CTLA4Ig into myeloid dendritic cells promotes their in vitro tolerogenicity and survival in allogeneic recipients Gene Therapy 1999 6: 554–563
Lee WC et al. Phenotype, function and in vivo migration and survival of allogeneic dendritic cell progenitors genetically engineered to express TGFβ Transplantation 1998 66: 1810–1817
Takayama T et al. Retroviral delivery of viral IL-10 into myeloid dendritic cells markedly inhibits their allostimulatory activity and promotes the induction of T cell hyporesponsiveness Transplantation 1998 66: 1567–1574
Zhang H et al. Induction of specific T cell tolerance by Fas ligand-expressing antigen-presenting cells J Immunol 1999 162: 1423–1430
Zhang HG et al. Induction of specific T-cell tolerance by adenovirus-transfected, Fas ligand-producing antigen presenting cells Nat Biotechnol 1998 16: 1045–1049
Nagata S . Fas-mediated apoptosis Adv Exp Med Biol 1996 406: 119–124
Nagata S . Fas-induced apoptosis Intern Med 1998 37: 179–181
Kabelitz D . Apoptosis, graft rejection, and transplantation tolerance Transplantation 1998 65: 869–875
Ferguson TA, Griffith TS . A vision of cell death: insights into immune privilege Immunol Rev 1997 156: 167–184
Lau HT, Yu M, Fontana A, Stoeckert CJ Jr . Prevention of islet allograft rejection with engineered myoblasts expressing FasL in mice Science 1996 273: 109–112
Chervonsky AV et al. The role of Fas in autoimmune diabetes Cell 1997 89: 17–24
Kang SM et al. Fas ligand expression in islets of Langerhans does not confer immune privilege and instead targets them for rapid destruction Nature Med 1997 3: 738–743
Stuart PM et al. CD95 ligand (FasL)-induced apoptosis is necessary for corneal allograft survival J Clin Invest 1997 99: 396–402
Fandrich F et al. CD95L confers immune priviledge to liver grafts which are spontaneously accepted Transplant Proc 1998 30: 1057–1058
Li XK et al. Prolonged survival of recipient rats with Fas-ligand-transfected liver allografts by using HVJ-liposome Transplant Proc 1998 30: 943
Suda T et al. Membrane Fas ligand kills human peripheral blood T lymphocytes, and soluble Fas ligand blocks the killing J Exp Med 1997 186: 2045–2050
Swenson KM et al. Fas ligand gene transfer to renal allografts in rats: effects on allograft survival Transplantation 1998 65: 155–160
Hanabuchi S et al. Fas and its ligand in a general mechanism of T-cell-mediated cytotoxicity Proc Natl Acad Sci USA 1994 91: 4930–4934
Chinnaiyan AM, O’Rourke K, Tewari M, Dixit VM . FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis Cell 1995 81: 505–512
Zhang J et al. Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mort1 Nature 1998 392: 296–300
Ray CA et al. Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme Cell 1992 69: 597–604
Itoh N, Tsujimoto Y, Nagata S . Effect of bcl-2 on Fas antigen-mediated cell death J Immunol 1993 151: 621–627
Tsujimoto Y et al. Bcl-2 and Bcl-xL block apoptosis as well as necrosis: possible involvement of common mediators in apoptotic and necrotic signal transduction pathways Leukemia 1997 11 (Suppl. 3): 380–382
Shimizu S et al. Induction of apoptosis as well as necrosis by hypoxia and predominant prevention of apoptosis by Bcl-2 and Bcl-XL Cancer Res 1996 56: 2161–2166
Shimizu S et al. Bcl-2 expression prevents activation of the ICE protease cascade Oncogene 1996 12: 2251–2257
Yoshimura S et al. Ceramide formation leads to caspase-3 activation during hypoxic PC12 cell death. Inhibitory effects of Bcl-2 on ceramide formation and caspase-3 activation J Biol Chem 1998 273: 6921–6927
Shimizu S et al. Bcl-2 prevents apoptotic mitochondrial dysfunction by regulating proton flux Proc Natl Acad Sci USA 1998 95: 1455–1459
Kondo S et al. Transfection with a bcl-2 expression vector protects transplanted bone marrow from chemotherapy-induced myelosuppression Cancer Res 1994 54: 2928–2933
Yamabe K et al. Prevention of hypoxic liver cell necrosis by in vivo human bcl-2 gene transfection Biochem Biophys Res Commun 1998 243: 217–223
Platt JL . New directions for organ transplantation Nature 1998 392: 11–17
Platt JL . Approaching the clinical application of xenotransplantation Am J Med Sci 1997 313: 315–321
Platt JL . A perspective on xenograft rejection and accommodation Immunol Rev 1994 141: 127–149
Lin SS et al. The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants J Clin Invest 1998 101: 1745–1756
Cotterell AH et al. The humoral immune response in humans following cross-perfusion of porcine organs Transplantation 1995 60: 861–868
Leventhal JR et al. Removal of baboon and human antiporcine IgG and IgM natural antibodies by immunoadsorption. Results of in vitro and in vivo studies Transplantation 1995 59: 294–300
Sandrin MS et al. Enzymatic remodelling of the carbohydrate surface of a xenogenic cell substantially reduces human antibody binding and complement-mediated cytolysis (see comments) Nature Med 1995 1: 1261–1267
McKenzie IF et al. Strategies to overcome the anti-Gal alpha (1–3)Gal reaction in xenotransplantation Transplant Proc 1996 28: 537
Takahashi T, Saadi S, Platt JL . Recent advances in the immunology of xenotransplantation Immunol Res 1997 16: 273–297
Schmoeckel M et al. Orthotopic heart transplantation in a transgenic pig-to-primate model Transplantation 1998 65: 1570–1577
Byrne GW et al. Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement-mediated damage Transplantation 1997 63: 149–155
Pruitt SK et al. The effect of soluble complement receptor type 1 on hyperacute xenograft rejection Transplantation 1991 52: 868–873
Osman N et al. Combined transgenic expression of alpha-galactosidase and alpha,2-fucosyltransferase leads to optimal reduction in the major xenoepitope Galalpha(1,3)Gal Proc Natl Acad Sci USA 1997 94: 14677–14682
Sandrin MS, Osman N, McKenzie IF . Transgenic approaches for the reduction of Galalpha(1,3)Gal for xenotransplantation Front Biosci 1997 2: e1–e11
Campbell KH, Loi P, Otaegui PJ, Wilmut I . Cell cycle co-ordination in embryo cloning by nuclear transfer Rev Reprod 1996 1: 40–46
Wakayama et al. Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei Nature 1998 394: 369–374
Bracy JL, Sachs DH, Iacomini J . Inhibition of xenoreactive natural antibody production by retroviral gene therapy Science 1998 281: 1845–1847
Petersson E et al. Allogeneic heart transplantation activates alloreactive NK cells Cell Immunol 1997 175: 25–32
Tran TH et al. Regulated and endothelial cell-specific expression of Fas ligand: an in vitro model for a strategy aiming at inhibiting xenograft rejection Transplantation 1998 66: 1126–1131
Acknowledgements
The authors would like to acknowledge the insightful comments of Dr Adrian Morelli on this review. This work was supported in part by Public Health Services grant DK 44935 to PDR and AI 41011 to AWT. NG is a recipient of a postdoctoral fellowship award from the Juvenile Diabetes Foundation International as well as a prize from the Fonds pour la formation de chercheurs et a l’aide a la recherche (Fonds FCAR) from the provincial government of Quebec, Canada.
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Giannoukakis, N., Thomson, A. & Robbins, P. Gene therapy in transplantation. Gene Ther 6, 1499–1511 (1999). https://doi.org/10.1038/sj.gt.3300981
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DOI: https://doi.org/10.1038/sj.gt.3300981