Immunological Determinants of Liver Transplant Outcomes Uncovered by the Rat Model.


:For many individuals suffering from end-stage liver disease (ESLD), the only treatment option is liver transplantation. However, liver transplant rejection is observed in 24-80% of transplant patients and lifelong drug regimens that follow the transplant procedure lead to serious side effects. Furthermore, the pool of donor livers available for transplantation is far less than the demand. Well-characterized and physiologically relevant models of liver transplantation are crucial to a deeper understanding of the cellular processes governing the outcomes of liver transplantation and serve as platform for testing new therapeutic strategies to enhance graft acceptance. Such a model has been found in the rat transplant model which has an advantageous size for surgical procedure, similar post-operative immunological progression and high genome match to the human liver. From rat liver transplant studies published in the last 5 years, it is clear that the rat model serves as a strong platform to elucidate transplant immunological mechanisms. Using the model, we have begun to uncover potential players and possible therapeutic targets to restore liver tolerance and preserve host immunocompetence. Here, we present an overview of recent literature for rat liver transplant models, with an aim to highlight the value of the models and to provide future perspectives on how these models could be further characterized to enhance the overall value of rat models to the field of liver transplantation.






Wang X,MacParland SA,Perciani CT




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2021-01-06 00:00:00








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  • Tacrolimus or cyclosporine: which is the better partner for mycophenolate mofetil in heart transplant recipients?

    abstract:BACKGROUND:The aim of this single-center study was to investigate whether trough level adjusted mycophenolate mofetil (MMF) is more efficacious in combination with tacrolimus (TAC) or cyclosporine (CsA) and to evaluate the impact of either drug on MMF dosage. METHODS:Sixty patients (TAC, n = 30; CsA, n = 30) undergoin...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Meiser BM,Groetzner J,Kaczmarek I,Landwehr P,Müller M,Jung S,Uberfuhr P,Fraunberger P,Stempfle HU,Weis M,Reichart B

    更新日期:2004-08-27 00:00:00

  • Hyperacute rejection in an ex vivo model of renal xenografting. Role of the mediator response and its pharmacologic manipulation by the specific platelet-activating factor antagonist WEB 2086BS.

    abstract::The pharmacologic modulation of the platelet-activating factor antagonist WEB 2086BS on the release of metabolites of the arachidonic acid and the cytokine TNF alpha was investigated in an ex vivo xenograft model of hyperacute rejection. Pig kidneys were perfused for 60 min in a perfusion system with oxygenated hepari...


    pub_type: 杂志文章


    authors: Saumweber DM,Bergmann R,Gokel M,Hammer C

    更新日期:1994-02-01 00:00:00

  • The regulatory/cytotoxic graft-infiltrating T cells differentiate renal allograft borderline change from acute rejection.

    abstract::The interpretation of cellular infiltrate from renal transplant recipients with borderline (BL) changes is still a challenging problem. To analyze the immune phenotype of such infiltrate, we quantified the mRNA expression of Foxp3 and interleukinL-10 and granzyme B (GB) in 15 kidney biopsies with BL changes. Controls ...


    pub_type: 杂志文章


    authors: Grimbert P,Mansour H,Desvaux D,Roudot-Thoraval F,Audard V,Dahan K,Berrehar F,Dehoulle-Poillet C,Farcet JP,Lang P,Le Gouvello S

    更新日期:2007-02-15 00:00:00

  • Sirolimus reduces the incidence of acute rejection episodes despite lower cyclosporine doses in caucasian recipients of mismatched primary renal allografts: a phase II trial. Rapamune Study Group.

    abstract:BACKGROUND:The novel agent sirolimus (SRL; Rapamune; rapamycin) inhibits the immune response by a mechanism distinct from those of calcineurin antagonists or antimetabolites. This randomized, controlled, multicenter, single blind, phase II trial examined the combination of SRL, steroids, and full versus reduced doses o...


    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验


    authors: Kahan BD,Julian BA,Pescovitz MD,Vanrenterghem Y,Neylan J

    更新日期:1999-11-27 00:00:00

  • Early immune reaction after reduced-intensity cord-blood transplantation for adult patients.

    abstract:BACKGROUND:To investigate immune reactions after reduced-intensity cord-blood transplantation (RI-CBT). MATERIALS AND METHODS:We reviewed medical records of 57 adult RI-CBT recipients. Preparative regimen comprised fludarabine, total-body irradiation, and either melphalan (n=51) or busulfan (n=6). Graft-versus-host di...


    pub_type: 杂志文章


    authors: Kishi Y,Kami M,Miyakoshi S,Kanda Y,Murashige N,Teshima T,Kusumi E,Hara S,Matsumura T,Yuji K,Masuoka K,Wake A,Morinaga S,Kanemaru M,Hayashi T,Tanaka Y,Taniguchi S,Tokyo Stem Cell Transplant Consortium.

    更新日期:2005-07-15 00:00:00

  • Attenuation of ischemia-reperfusion injury of the liver in dogs by cyclosporine. A comparative study with allopurinol and methylprednisolone.

    abstract::The effects of pretreatment with cyclosporine, allopurinol, or methylprednisolone on ischemia-reperfusion injury of the liver were investigated. A total of 32 adult mongrel dogs that received one of the pretreatments were divided into four groups and were subjected to 90 min liver ischemia. Serum activities of asparta...


    pub_type: 杂志文章


    authors: Yamanoi A,Nagasue N,Kohno H,Chang YC,Hayashi T,Nakamura T

    更新日期:1991-07-01 00:00:00

  • HLA-G is a crucial immunosuppressive molecule secreted by adult human mesenchymal stem cells.

    abstract::Adult bone marrow-derived mesenchymal stem cells (MSCs) are multipotential cells capable of regenerating injured tissues. In addition to their multipotency, MSCs inhibit natural killer cell cytotoxicity and T-lymphocyte alloproliferation. Several immunosuppressive mechanisms have been described, including indoleamine ...


    pub_type: 杂志文章


    authors: Selmani Z,Naji A,Gaiffe E,Obert L,Tiberghien P,Rouas-Freiss N,Carosella ED,Deschaseaux F

    更新日期:2009-05-15 00:00:00

  • Biopsy diagnosis and clinical outcome of persistent focal pulmonary lesions after marrow transplantation.

    abstract::We reviewed the results of all percutaneous fine needle aspirations (FNA) and open lung biopsies (OLB) after bone marrow transplantation at our center (1984-1987) for the evaluation of focal lung lesions that developed or persisted despite antibiotic administration. We sought to determine the prevalence and types of i...


    pub_type: 杂志文章


    authors: Crawford SW,Hackman RC,Clark JG

    更新日期:1989-08-01 00:00:00

  • Screening for de novo anti-human leukocyte antigen antibodies in nonsensitized kidney transplant recipients does not predict acute rejection.

    abstract:BACKGROUND:The purpose of this study was to determine whether screening for anti-human leukocyte antigen (HLA) antibodies (Abs) could predict development of acute rejection (AR) before clinical evidence of kidney allograft dysfunction in nonsensitized recipients. METHODS:Eighty-four non-HLA identical kidney transplant...


    pub_type: 杂志文章


    authors: Gill JS,Landsberg D,Johnston O,Shapiro RJ,Magil AB,Wu V,Tinckam K,Keown P

    更新日期:2010-01-27 00:00:00

  • Impact of cytochrome p450 3A5 genetic polymorphism on tacrolimus doses and concentration-to-dose ratio in renal transplant recipients.

    abstract:BACKGROUND:Tacrolimus pharmacokinetic characteristics vary greatly among individuals. Tacrolimus is a substrate of cytochrome p450 (CYP), of subfamily CYP3A. CYP3A activity is the sum of the activities of the family of CYP3A genes, including CYP3A5. Subjects with the CYP3A5*1/*1 genotype express large amounts of CYP3A5...


    pub_type: 杂志文章


    authors: Thervet E,Anglicheau D,King B,Schlageter MH,Cassinat B,Beaune P,Legendre C,Daly AK

    更新日期:2003-10-27 00:00:00

  • Promoting Organ Donor Registries Through Public Education: What Is the Cost of Securing Organ Donors?

    abstract:BACKGROUND:Transplant medicine's impact on America's public health is seriously limited by acute shortage of transplantable organs. Consequently, the United Sates has witnessed considerable investment in the promotion of organ donor registries. Although there is no evidence to support that donor registry promotion alle...


    pub_type: 杂志文章


    authors: Razdan M,Smith KJ,Bryce CL,Degenholtz HB

    更新日期:2016-06-01 00:00:00

  • Porcine endothelium supports transendothelial migration of human leukocyte subpopulations: anti-porcine vascular cell adhesion molecule antibodies as species-specific blockers of transendothelial monocyte and natural killer cell migration.

    abstract:BACKGROUND:In cases where hyperacute rejection has been prevented, pig to primate organ transplantation results in a delayed rejection mediated by graft-infiltrating leukocytes. The migration of human leukocytes across porcine endothelium is poorly characterized, but may offer targets for species-specific antirejection...


    pub_type: 杂志文章


    authors: Hauzenberger E,Hauzenberger D,Hultenby K,Holgersson J

    更新日期:2000-05-15 00:00:00

  • Comparative long-term evaluation of tacrolimus and cyclosporine in pediatric liver transplantation.

    abstract:BACKGROUND:In this report, we compare the long-term outcome of pediatric liver transplantation (LTx) patients maintained with tacrolimus-based and with cyclosporine (CsA)-based immunosuppressive therapy. We examine long-term patient and graft survival, the incidence of rejection, and immunosuppression-related complicat...


    pub_type: 杂志文章


    authors: Jain A,Mazariegos G,Kashyap R,Green M,Gronsky C,Starzl TE,Fung J,Reyes J

    更新日期:2000-08-27 00:00:00

  • Association of cytomegalovirus genotype with graft rejection after liver transplantation.

    abstract:BACKGROUND:The envelope glycoprotein gB of human cytomegalovirus (CMV) occurs as one of four main genotypes. Some previous studies have proposed a relationship of CMV gB genotype to the frequency of symptomatic infection and to clinical outcomes in both transplant and human immunodeficiency virus-infected populations. ...


    pub_type: 杂志文章


    authors: Rosen HR,Corless CL,Rabkin J,Chou S

    更新日期:1998-12-27 00:00:00

  • Comparison of activation requirements and activation phenotype of allogeneic and xenogeneic rodent responses in vivo and in vitro.

    abstract:BACKGROUND:Both discordant and concordant xenogeneic responses are dominated by humoral immunity. Recent advances in molecular engineering approaches may largely prevent rejection by means of this pathway, leaving the cellular arm of the immune response as the principal remaining barrier to successful engraftment. MET...


    pub_type: 杂志文章


    authors: Trani JL,Song HK,Lerner SM,Markmann JW,Barker CF,Naji A,Markmann JF

    更新日期:2001-08-15 00:00:00

  • Tolerance induction in a fully allogeneic combination using anti-T cell receptor-alpha beta monoclonal antibody, low dose irradiation, and donor bone marrow transfusion.

    abstract::In a murine strain combination disparate in both H-2 antigens and minor histocompatibility antigens consisting of C57BL/6 (B6; H-2b, Mls-1b) mice as recipients and AKR/J (AKR; H-2k, Mls-1a) mice as donors, we reported that the administration of anti-TCR-alpha beta mAb nonspecifically suppresses the ability to reject a...


    pub_type: 杂志文章


    authors: Nomoto K,Yung-Yun K,Omoto K,Umesue M,Murakami Y,Matsuzaki G,Nomoto K

    更新日期:1995-02-15 00:00:00

  • Thymoglobulin versus ATGAM induction therapy in pediatric kidney transplant recipients: a single-center report.

    abstract:BACKGROUND:Induction immunosuppressive therapy with the anti-T-cell antibody Thymoglobulin decreases the incidence of acute rejection in adult kidney transplant (KTx) recipients, but limited data are available for pediatric KTx recipients. METHODS:We conducted a historical cohort study to compare rates of survival, re...


    pub_type: 临床试验,杂志文章


    authors: Khositseth S,Matas A,Cook ME,Gillingham KJ,Chavers BM

    更新日期:2005-04-27 00:00:00

  • Optimal Outcomes in Young Class 3 Patients With Thalassemia Undergoing HLA-Identical Sibling Bone Marrow Transplantation.

    abstract:BACKGROUND:Bone marrow transplantation (BMT) for class 3 patients with thalassemia is challenging due to high rates of graft rejection and transplant-related mortality. Since the first studies of BMT in the late 1980s, a number of conditioning regimens have been designed to improve outcomes, but with suboptimal results...


    pub_type: 杂志文章


    authors: Gaziev J,Isgrò A,Sodani P,Marziali M,Paciaroni K,Gallucci C,De Angelis G,Andreani M,Testi M,Alfieri C,Ribersani M,Galluccio T,Battarra MR,Morrone A,Lucarelli G

    更新日期:2016-04-01 00:00:00

  • Atypical mixed lymphocyte culture. Identity between mother and child in leukemia and aplastic anemia.

    abstract::The mixed lymphocyte culture tests between one patient with acute lymphocytic leukemia and her mother and between another patient with aplastic anemia and his mother were found nonreactive, despite a one-haplotype difference for HL-A. Two crossovers in each family at the MLC locus or a specific defect in lymphocyte r...


    pub_type: 杂志文章


    authors: Opelz G

    更新日期:1975-01-01 00:00:00

  • Increased risk of graft failure in kidney transplant recipients after a diagnosis of dyspepsia or gastroesophageal reflux disease.

    abstract:BACKGROUND:Gastrointestinal complications are common in patients who undergo kidney transplantation and may affect posttransplant outcomes. We examined the incidence and predictors of gastroesophageal reflux disease (GERD) and dyspepsia and their associations with graft survival and mortality after transplant. METHODS...


    pub_type: 杂志文章


    authors: Neri L,Rocca Rey LA,Pinsky BW,Lentine KL,Salvalaggio PR,Machnicki G,Willoughby L,Burroughs TE,Takemoto SK,Schnitzler MA

    更新日期:2008-02-15 00:00:00

  • Preliminary experience with renal transplantation in HIV+ recipients: low acute rejection and infection rates.

    abstract:BACKGROUND:Only four centers have reported their results with renal transplantation in human immunodeficiency virus (HIV)+ recipients on highly active antiretroviral therapy, and acute rejection (AR) rates have consistently ranged from 43% to 67%. METHODS:We examined the outcomes of eight adult HIV+ primary renal allo...


    pub_type: 杂志文章


    authors: Gruber SA,Doshi MD,Cincotta E,Brown KL,Singh A,Morawski K,Alangaden G,Chandrasekar P,Losanoff JE,West MS,El-Amm JM

    更新日期:2008-07-27 00:00:00

  • Prevention of insulitis and diabetes in nonobese diabetic mice by administration of FK506.

    abstract::We investigated the preventive effect of the immunosuppressive agent FK506 on autoimmune insulitis in nonobese diabetic mice. The mice were given FK506 in a dose of 1.0 mg/kg, every other day, from age 2 to 12, 2 to 6, and 4 to 12 weeks, respectively; after which, the incidence of insulitis and overt diabetes was moni...


    pub_type: 杂志文章


    authors: Kai N,Motojima K,Tsunoda T,Kanematsu T

    更新日期:1993-04-01 00:00:00

  • Immunoglobulin heavy chain transgenic mice expressing Galalpha(1,3)Gal-reactive antibodies.

    abstract:BACKGROUND:Natural antibodies that bind the carbohydrate antigen Galalpha1-3Galbeta1-4GlcNAc-R (alphaGal) mediate rigorous rejection of porcine xenografts and represent a major immunological hurdle to successful discordant xenotransplantation. However, little is known about how production of antibodies specific for alp...


    pub_type: 杂志文章


    authors: Cretin N,Iacomini J

    更新日期:2002-05-27 00:00:00

  • Autoimmunity after allogeneic bone marrow transplantation. A study of 53 long-term-surviving patients.

    abstract::Various autoantibodies were screened in 53 long-term survivors after allogeneic bone marrow transplantation. Among them, 40 displayed chronic graft-versus-host disease, with clinical features reminiscent of collagen diseases, especially scleroderma, Sjögren's syndrome, and autoimmune hepatitis. Antinuclear, anti-smoot...


    pub_type: 杂志文章


    authors: Rouquette-Gally AM,Boyeldieu D,Prost AC,Gluckman E

    更新日期:1988-08-01 00:00:00

  • Respiratory tract viral infections in bone marrow transplant patients.

    abstract:BACKGROUND:Community respiratory viruses such as respiratory syncytial virus (RSV), adenovirus, influenza A, influenza B, and the parainfluenza group are frequent causes of respiratory disease in bone marrow transplant (BMT) patients. MATERIAL AND METHODS:During the period from March 1993 to August 1999, 810 samples o...


    pub_type: 杂志文章


    authors: Raboni SM,Nogueira MB,Tsuchiya LR,Takahashi GA,Pereira LA,Pasquini R,Siqueira MM

    更新日期:2003-07-15 00:00:00

  • Phototherapy in the treatment of cutaneous graft-versus-host disease. Our preliminary experience in resistant patients.

    abstract::Graft-versus-host disease (GVHD)* is a frequent complication of allogeneic bone marrow transplantation. The potentially beneficial effect of phototherapy for treatment of cutaneous manifestations of GVHD led us to investigate retrospectively the effect of this therapy in a larger series of patients. Eleven patients wi...


    pub_type: 杂志文章


    authors: Aubin F,Brion A,Deconinck E,Plouvier E,Hervé P,Humbert P,Cahn JY

    更新日期:1995-01-15 00:00:00

  • Spontaneous reestablishment of self-tolerance in BB/Pfd rats.

    abstract::We describe a substrain of BB rats, BB/Pfd, characterized by a loss of autoimmune potential soon after onset of diabetes. When fresh syngeneic (BB/Pfd) islets (6 islets/g body weight) were transplanted under the kidney capsule of diabetic BB/Pfd rats 1-2 weeks after diabetes onset (n = 14), no recurrence of diabetes o...


    pub_type: 杂志文章


    authors: Mathieu C,Kuttler B,Waer M,Bouillon R,Hahn HJ

    更新日期:1994-08-15 00:00:00

  • Successful use of an enhanced immunosuppressive protocol with plasmapheresis for ABO-incompatible mismatched grafts in liver transplant recipients.

    abstract::Graft and patient survival rates after transplantation of ABO-incompatible liver allografts have been poor. We used plasmapheresis and a potent immunosuppressive regimen to control hemagglutinin levels and prevent early rejection. Ten patients who had a United Network for Organ Sharing status of 4 received ABO-incompa...


    pub_type: 杂志文章


    authors: Mor E,Skerrett D,Manzarbeitia C,Sheiner PA,Schwartz ME,Emre S,Thung SN,Miller CM

    更新日期:1995-04-15 00:00:00

  • Active role of chimerism in transplantation tolerance induced by antilymphocyte serum, sirolimus, and bone-marrow-cell infusion.

    abstract:BACKGROUND:A regimen consisting of antilymphocyte serum (ALS), sirolimus, and donor bone-marrow-cell (BMC) infusion induces indefinite skin allograft survival across fully mismatched mouse strain combinations. We investigated the role of chimerism in this transplantation tolerance model. MATERIALS:B10.A (H-2a) mice we...


    pub_type: 杂志文章


    authors: Kanamoto A,Monaco AP,Maki T

    更新日期:2004-09-27 00:00:00

  • Cardiac myosin autoantibodies and acute rejection after heart transplantation in patients with dilated cardiomyopathy.

    abstract:OBJECTIVES:To determine whether humoral autoimmune responses associated with dilated cardiomyopathy (DCM) influence the postoperative clinical course following cardiac transplantation. METHODS:ELISA levels of preformed cardiac myosin (CM) autoantibodies (Abs) in patients with a pretransplant diagnosis of dilated cardi...


    pub_type: 杂志文章


    authors: Warraich RS,Pomerance A,Stanley A,Banner NR,Dunn MJ,Yacoub MH

    更新日期:2000-04-27 00:00:00