Abstract:
BACKGROUND:Ischemia-reperfusion (I/R) injury is the major cause of delayed renal graft function in kidney transplantation. To date, there are no effective therapeutic approaches for preventing I/R injury. We previously reported that treatment of animals with small interference RNA (siRNA) would prevent warm I/R injury in nontransplant models and cold I/R injury in heart transplantation. In the present study, we further explore the feasibility of protecting grafts from extended cold I/R injury as applied to kidney transplantation by downregulating I/R-associated genes using siRNA. METHODS:Donor kidneys were intra-arterially perfused with siRNA containing solution during donor excision and preserved in siRNA containing solution. The siRNA-treated donor organs were then implanted into syngeneic recipient mice, and the 2 original kidneys were removed from the recipient. The effect of siRNA solution on extended cold I/R injury was determined by assessing renal function, histopathological change, cell apoptosis, and inflammation. RESULTS:The perfused siRNA solution knocked down the expression of complement 3, RelB, and Fas in the kidney at the mRNA and protein levels. Administration of siRNA solution reduced the levels of blood urea nitrogen and serum creatinine as compared with control groups. The siRNA cocktail decreased cell apoptosis and histopathological changes in the kidney and prolonged graft survival. The siRNA cocktail also reduced the expression of proinflammatory cytokines, IL-6, and TNFα. CONCLUSIONS:In conclusion, this is the first demonstration that perfusing donor organs with an siRNA cocktail solution can induce gene silencing in the kidney and prevent kidneys from extended cold I/R injury in kidney transplantation, highlighting the promise of the clinical application of siRNA-based therapies in the preservation of donor organs.
journal_name
Transplantationjournal_title
Transplantationauthors
Zheng X,Zang G,Jiang J,He W,Johnston NJ,Ling H,Chen R,Zhang X,Liu Y,Haig A,Luke P,Jevnikar AM,Min WPdoi
10.1097/TP.0000000000000960subject
Has Abstractpub_date
2016-04-01 00:00:00pages
743-52issue
4eissn
0041-1337issn
1534-6080pii
00007890-201604000-00014journal_volume
100pub_type
杂志文章相关文献
TRANSPLANTATION文献大全abstract:BACKGROUND:Kidneys from infectious risk donors (IRD) confer substantial survival benefit in adults, yet the benefit of IRD kidneys to pediatric candidates remains unclear in the context of high waitlist prioritization. METHODS:Using 2010-2016 Scientific Registry of Transplant Recipients data, we studied 2417 pediatric...
journal_title:Transplantation
pub_type: 杂志文章,多中心研究
doi:10.1097/TP.0000000000002674
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND:The role of human herpesvirus (HHV)-8 in the pathogenesis of multiple myeloma and its pre-malignant state of monoclonal gammopathy is unclear. HHV-8 is transmitted by organ transplantation, representing a unique model with which to investigate primary HHV-8 infection. METHODS:The authors studied the inciden...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000129065.31427.96
更新日期:2004-05-27 00:00:00
abstract:BACKGROUND:In a pig liver transplantation model, we compared the effects of Celsior solution (CS), an extracellular preservation solution, with Viaspan (University of Wisconsin solution, UW) on graft function and animal survival. METHODS:Pig livers were flushed with either CS or UW solution and cold-stored for 12 hr (...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-200106270-00005
更新日期:2001-06-27 00:00:00
abstract::We developed a new and simplified donor-specific blood transfusion (DSBT) protocol for prospective kidney transplant recipients from one-haplotype-mismatched related donors. Prospective kidney donors gave 450 ml of blood in a quad-pack unit, and the blood was stored in a blood bank. Twenty-five patients were transfuse...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198411000-00012
更新日期:1984-11-01 00:00:00
abstract::We report the largest single-center experience with extracorporeal photopheresis (ECP) for bronchiolitis obliterans syndrome (BOS) and recurrent acute rejection (AR) after lung transplantation. Lung transplant recipients undergoing ECP for BOS and recurrent AR were included (1997-2007). The rate of forced expiratory v...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e31818bc024
更新日期:2008-12-15 00:00:00
abstract:BACKGROUND:We previously reported that Lewis rat hearts transplanted into BALB/c mice developed typical acute vascular rejection (AVR). The present study was undertaken to determine the efficacy of LF15-0195, a new analogue of 15-deoxyspergualin, in the prevention of AVR and to determine whether a combination of LF15-0...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.TP.0000057245.59998.95
更新日期:2003-05-15 00:00:00
abstract:BACKGROUND:CD154 mediates key facets of humoral and cellular immunity to alloantigens, and is tolerogenic to influenza antigens in primates. Barriers to CD154-based tolerance induction for primate cardiac allografts have not previously been defined. METHODS:Heterotopic cardiac allograft outcomes in cynomolgus monkeys ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000190099.62847.e6
更新日期:2006-01-27 00:00:00
abstract:BACKGROUND:African American kidney transplant recipients generally exhibit poor long-term graft survival compared with other ethnic groups. The combination of sirolimus, tacrolimus, and corticosteroids has proven to be effective in reducing rejection episodes in high-risk organ and islet cell transplant recipients but ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-200207270-00008
更新日期:2002-07-27 00:00:00
abstract::In the DA-to-Lewis renal allograft model, donor whole blood enhanced renal allograft survival (14.5 +/- 7.6 days versus 6.9 +/- 0.6 days in controls [P less than 0.01]). The effect of individual cell components given in numbers equivalent to those present in the enhancing volumes of donor whole blood was studied. Immu...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198409000-00003
更新日期:1984-09-01 00:00:00
abstract::A series of three synthetic peptides spanning H-2E alpha k chain residues (90-110), (110-130), and (130-150) were synthesized and purified. Mice representative of H-2E- (B6, B10, B10.M, B10.Q, B10.S) and H-2E+ (B10.D2, B10.K, B10.RIII) were immunized with individual peptides and lymph node cells challenged in vitro. B...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199211000-00029
更新日期:1992-11-01 00:00:00
abstract::Non-A, non-B hepatitis is a significant cause of liver disease among renal allograft recipients. In order to assess the impact and prevalence of hepatitis C in a series of renal allograft recipients, we retrospectively screened 621 consecutive patients transplanted between 1979 and 1989 and 484 cadaver organ donors re...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199102000-00024
更新日期:1991-02-01 00:00:00
abstract:BACKGROUND:This study addresses the question of the mechanism for maintaining tolerance to donor alloantigen in the absence of antigen and the role of secondary lymphoid tissues. METHODS:Depleting anti-CD4 antibody administration in conjunction with allogeneic heart transplantation generates donor-specific operational...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000259928.16003.aa
更新日期:2007-05-15 00:00:00
abstract::Governmental and private programs that pay next of kin who give permission for the removal of their deceased relative's organs for transplantation exist in a number of countries. Such payments, which may be given to the relatives or paid directly for funeral expenses or hospital bills unrelated to being a donor, aim t...
journal_title:Transplantation
pub_type: 指南,杂志文章
doi:10.1097/TP.0000000000001198
更新日期:2016-09-01 00:00:00
abstract::We performed a multicenter study to investigate the problem of cadaver kidney transplants that never achieve function, or that recover after a period of delayed function, and we used multivariate techniques to model the results. Sixty-nine patients who received cadaver kidney transplants that never functioned (NF) wer...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198801000-00027
更新日期:1988-01-01 00:00:00
abstract:BACKGROUND:Ischemia-reperfusion (I/R) injury is a multifactorial phenomenon that occurs during the transplant event and frequently compromises early graft function after liver transplantation (LT). Current comprehension of molecular mechanisms and regulation processes of I/R injury lacks clarity. MicroRNA (miRNA) regul...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e3182a20398
更新日期:2013-11-27 00:00:00
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...
journal_title:Transplantation
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1097/00007890-199911270-00016
更新日期:1999-11-27 00:00:00
abstract::To test the importance of B lymphocytes in immunity to major histocompatibility complex class I alloantigens, B cell-deficient mice were generated by reconstituting severe combined immunodeficiency mice, which lack functional B and T lymphocytes, with T cells or with both T and B cells. The reconstituted mice were cha...
journal_title:Transplantation
pub_type: 杂志文章
doi:
更新日期:1993-06-01 00:00:00
abstract::Graft-versus-host disease (GvHD), a life-threatening complication of bone marrow transplantation, is initiated by donor T cells reacting to recipient dendritic cells (DC). GvHD can be controlled by attenuating donor T cells, but few strategies exist to target DC, particularly resident tissue DC, despite recent evidenc...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000149321.86104.c4
更新日期:2005-03-27 00:00:00
abstract::A 22-year-old previously nonsensitized female patient (HLA-A2,28; B7,14; DR1,2) received a kidney from her HLA-identical brother. She irreversibly rejected the graft 2 1/2 weeks later. In vitro tests performed 6 weeks after the graft loss, using recipient responding and donor-stimulating and target cells, revealed a w...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198201000-00011
更新日期:1982-01-01 00:00:00
abstract::To determine the impact of different flush and reperfusion techniques on postreperfusion syndrome (PRS) and postoperative graft function, 100 transplants were randomly assigned into four groups as follows: group 1 (n=31), portal vein flush, no vena caval venting; group 2 (n=21), hepatic arterial flush, no vena caval v...
journal_title:Transplantation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00007890-199702150-00012
更新日期:1997-02-15 00:00:00
abstract::Several groups have reported technical complications and poor graft survival rates in kidney transplants from pediatric donors to adult recipients. Increased incidences of acute rejections, vascular thrombosis, and early glomerulosclerotic lesions have led many groups to abandon this graft combination. Over the last 4...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199601150-00009
更新日期:1996-01-15 00:00:00
abstract::The success of kidney transplants is limited by the lack of robust improvements in long-term survival. It is now recognized that alloimmune responses are responsible for the majority of allograft failures. Development of novel therapies to decrease allosensitization is critical. The lack of new drug development in kid...
journal_title:Transplantation
pub_type: 杂志文章,评审
doi:10.1097/TP.0000000000001452
更新日期:2017-01-01 00:00:00
abstract::Since calcium channel blocking agents and CsA exert an antiproliferative effect upon T cell mitogenesis, we have compared and characterized their immunosuppressive properties at the level of gene activation. Verapamil (greater than or equal to 30 microM), which blocks T cell mitogenesis and a rise in cytosolic calcium...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198902000-00029
更新日期:1989-02-01 00:00:00
abstract::Arterial ketone body ratio (AKBR [acetoacetate/beta-hydroxybutyrate]) was measured in nineteen patients under medical supportive therapy for fulminant hepatic failure (FHF), in order to evaluate its predictive value relative to liver transplantation. Of the 19 patients 8 (42%) were salvaged and 11 (58%) died. Seven of...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199104000-00009
更新日期:1991-04-01 00:00:00
abstract:BACKGROUND:FK506-binding proteins (FKBP) are immunophilins that interact with the immunosuppressive drugs FK506 and rapamycin. Several FKBP family members such as FKBP12, FKBP12.6, and FKBP51 are expressed in T cells. It has been speculated that these FKBPs are possibly redundant in the immunosuppressant-induced T-cell...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-200206150-00023
更新日期:2002-06-15 00:00:00
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...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.TP.0000090753.99170.89
更新日期:2003-10-27 00:00:00
abstract::The effect of pretreatment with cyclosporine on liver preservation was studied using a rat liver transplant model. In a preliminary 1-week survival study, 59 liver transplants were performed. In group A, neither donors nor recipients were treated. In group B, the recipients were pretreated by a 3-day course of CsA (10...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199110000-00007
更新日期:1991-10-01 00:00:00
abstract:BACKGROUND:The role of asymptomatic bacteriuria in kidney transplant recipients is unknown. There is no clear evidence of its effect on transplanted kidney. METHODS:We studied urine cytokines profile among kidney transplant recipients with bacteriuria found in screening examination. Urine cultures were collected in 26...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000226072.20185.f8
更新日期:2006-06-27 00:00:00
abstract::If transplantation of endocrine tissue is to become a therapy for a significant number of insulin-dependent diabetic individuals, tissue sources other than adult human islets will be required. Because human fetal pancreatic cells may offer that alternative, we have tried to find the optimal combination of tissue cultu...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199312000-00011
更新日期:1993-12-01 00:00:00
abstract:BACKGROUND:T-cell activation through T-cell receptor engagement requires co-stimulatory molecules and also adhesion molecules such as ICAM-1. Moreover ICAM-1 mediates leukocyte invasion from the blood into tissue during inflammatory processes. In animal studies using mouse monoclonal antibodies against ICAM-1 (enlimoma...
journal_title:Transplantation
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1097/00007890-199903150-00015
更新日期:1999-03-15 00:00:00