Abstract:
:Type I diabetes mellitus (TID) results from the autoimmune destruction of the insulin-producing pancreatic β-cells. Gene therapy is one strategy being actively explored to cure TID by affording non-β-cells the ability to secrete insulin in response to physiologic stimuli. In previous studies, we used a novel surgical technique to express furin-cleavable human insulin (INS-FUR) in the livers of streptozotocin (STZ)-diabetic Wistar rats and nonobese diabetic (NOD) mice with the use of the HMD lentiviral vector. Normoglycemia was observed for 500 and 150 days, respectively (experimental end points). Additionally, some endocrine transdifferentiation of the liver, with storage of insulin in granules, and expression of some β-cell transcription factors (eg, Pdx1, Neurod1, Neurog3, Nkx2-2, Pax4) and pancreatic hormones in both studies. The aim of this study was to determine if this novel approach could induce liver to pancreatic transdifferentiation to reverse diabetes in pancreatectomized Westran pigs. Nine pigs were used in the study, however only one pig maintained normal fasting blood glucose levels for the period from 10 to 44 days (experimental end point). This animal was given 2.8 × 10(9) transducing units/kg of the lentiviral vector expressing INS-FUR. A normal intravenous glucose tolerance test was achieved at 30 days. Reverse-transcription polymerase chain reaction analysis of the liver tissue revealed expression of several β-cell transcription factors, including the key factors, Pdx-1 and Neurod1, pancreatic hormones, glucagon, and somatostatin; however, endogenous pig insulin was not expressed. Triple immunofluorescence showed extensive insulin expression, as was previously observed in our studies with rodents. Additionally, a small amount of glucagon and somatostatin protein expression was seen. Collectively, these data indicate that pancreatic transdifferentiation of the liver tissue had occurred. Our data suggest that this regimen may ultimately be used clinically to cure TID, however more work is required to replicate the successful reversal of diabetes in increased numbers of pigs.
journal_name
Transplant Procjournal_title
Transplantation proceedingsauthors
Gerace D,Ren B,Hawthorne WJ,Byrne MR,Phillips PM,O'Brien BA,Nassif N,Alexander IE,Simpson AMdoi
10.1016/j.transproceed.2013.01.051subject
Has Abstractpub_date
2013-06-01 00:00:00pages
1869-74issue
5eissn
0041-1345issn
1873-2623pii
S0041-1345(13)00082-1journal_volume
45pub_type
杂志文章abstract:OBJECTIVES:The aim of this retrospective study was to assess the incidence of acute rejection episodes (AR), diabetes mellitus (DM), and serum creatinine (SCr) among renal transplant recipients treated with tacrolimus (Tac), steroids (S), and mycophenolate mofetil (MMF) or azathioprine (Aza). METHODS:Seventy-five rena...
journal_title:Transplantation proceedings
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0041-1345(03)00815-7
更新日期:2003-09-01 00:00:00
abstract::In a retrospective study we analyzed the incidence and characteristics of de novo tumors developing in renal transplant recipients treated in our center. The 5% incidence de novo tumors developing among patients treated with azathioprine and prednisolone (n = 241) was similar to the 5.4% incidence of de novo tumors de...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/s0041-1345(03)00472-x
更新日期:2003-06-01 00:00:00
abstract::Mass-scale production of hepatocytes from human induced pluripotent stem cells (iPSCs) with functional properties of primary hepatocytes is of great value in clinical transplantation for liver failure as well as in facilitating drug development by predicting humanized drug metabolism profiles. In this report, we gener...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2013.12.021
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND:The exact cause and appropriate treatment for cholestasis following liver transplantation in recipients with hepatitis C virus recurrence (RHCV) are difficult to determine. Our objective was to determine the diagnostic accuracy of clinical and histological parameters in liver transplant recipients with RHCV ...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2005.10.012
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND:The dialysis delivered after a chronic kidney disease (CDK) or any otherwise severe end-stage renal failure is a complex medical task, leading to major medical and psychopathological distress for the patient. The aim of the present study was to analyze the impact of the dialysis experience on the nephrologic...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2014.07.026
更新日期:2014-09-01 00:00:00
abstract::Mitomycin-C (MMC) is categorized as an agent that causes genotoxic stress by triggering various intracellular signaling pathways. We have previously shown that MMC pretreatment of highly immunogenic crude islets leads to significant prolongation of graft survival in a rat-to-mouse model. In the present study, we exami...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2004.04.029
更新日期:2004-05-01 00:00:00
abstract:OBJECTIVE:We evaluated the incidence of urological complications after simultaneous renal and pancreatic transplantation. PATIENTS AND METHODS:We retrospectively reviewed urological complications following 107 simultaneous kidney-pancreas transplantations performed at our institution between March 1995 and June 2008. ...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2009.06.065
更新日期:2009-07-01 00:00:00
abstract::Liver transplantation for the treatment of patients with advanced liver disease is organized according to a waiting list taking into account different criteria. The agreed distribution model in Andalusia assumes that sometimes an organ is extracted in a different province to that where the implantation is to be perfor...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2013.10.032
更新日期:2013-01-01 00:00:00
abstract::Anastomosing the renal artery and vein in transplant recipients without a cooling mechanism exposes the kidney to temperatures exceeding the metabolic threshold (15°C to 18°C), at which the protective effects of renal hypothermia are lost. This anastomotic time, or second warm ischemic time, can be deleterious to graf...
journal_title:Transplantation proceedings
pub_type: 杂志文章,评审
doi:10.1016/j.transproceed.2018.09.003
更新日期:2018-12-01 00:00:00
abstract::This article seeks to standardize an experimental model of liver ischemia-reperfusion in rats following hemorrhagic shock modulated by N-acetylcysteine (NAC). Twenty-seven adult Wistar rats were randomized into three groups: the HS-IR-Garm underwent hemorrhagic shock with selective hepatic ischemia followed by reperfu...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2004.03.047
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND:In renal transplantation, the degree of HLA matching has been reported to be negatively correlated with graft loss, with the number of rejections with complications. This association is less clear in heart transplantation, where there are contradictory studies, although most are consistent with those in rena...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2005.09.145
更新日期:2005-11-01 00:00:00
abstract::Understanding specific tolerance mechanisms is a primary goal of transplantation science. We have previously shown that hosts treated with MHC class I protein have donor sequences in the alpha1-helix of the alpha1 domain on a background of self-epitopes, resulting in the development of donor-specific tolerance. Howeve...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2005.02.114
更新日期:2005-05-01 00:00:00
abstract::The first clinical orthotopic liver transplantation in Brazil was performed on August 5, 1968. The patient was awake after surgery and died on the seventh postoperative day due to subdural hematoma, bronchopneumonia, renal failure, and graft rejection. The report of this case is important to understand the evolution o...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2004.03.096
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND:The Charlson Comorbidity Index for orthotopic liver transplantation (CCI-OLT) is a modified clinical score recently proposed to be useful for the assessment of long-term survival after OLT. It includes 9 associated conditions selected upon a multivariate analysis of a large cohort of transplant recipients. I...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2009.07.097
更新日期:2009-10-01 00:00:00
abstract::Following adoptive transfer into irradiated recipients, thymocytes can be induced to respond strongly to vaccinia virus. High levels of cytotoxic T-lymphocyte (CTL) activity may be generated from thymus, but not from spleen, of 3-day-old mice. The capacity of thymocytes to differentiate into effector CTL tends to be l...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:
更新日期:1981-12-01 00:00:00
abstract:OBJECTIVE:To evaluate relevant arterial, hepatic, and portal venous anatomy using multidetector computed tomography (CT) angiography in potential living liver donors at a single liver transplantation center in China. METHODS:One hundred two consecutive potential liver donors underwent CT angiography in the arterial, p...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2008.08.031
更新日期:2008-10-01 00:00:00
abstract:INTRODUCTION:Cardiovascular disease is more common in renal transplant recipients (RTRs) than in the general population, and is the major cause of both graft loss and patient death in RTRs. OBJECTIVES:This study aimed to characterize the cardiovascular risk factors, calculate the 7-year risk for major adverse cardiac ...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2015.03.031
更新日期:2015-05-01 00:00:00
abstract:UNLABELLED:We have previously reported that tolerance to class I disparate lung allografts in miniature swine could be induced using an intensive 12-day course of tacrolimus and that pretransplant sensitization with immunogenic MHC class I allopeptides failed to block the induction of tolerance. We also have previously...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2006.10.064
更新日期:2006-12-01 00:00:00
abstract::Alcoholic liver disease (ALD) is a leading indication for liver transplantation (LT) in Western countries. The rate of resumption of alcohol abuse is 7% to 95% after LT for ALD. A high prevalence of alcohol abuse has been observed in disaster-exposed populations; however, little is known about the association between ...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2013.09.048
更新日期:2014-04-01 00:00:00
abstract:PURPOSE:We aimed to determine the visibility of bile ducts of the caudate lobe (B1s) and right/left (R/L) dissociation on contrast-enhanced T1-magentic resonance cholangiography after gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid administration (CE-T1-MRC) in live liver donors. MATERIALS AND METHODS:In 30...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2019.04.085
更新日期:2019-10-01 00:00:00
abstract::The development of a small animal model for hepatitis C virus (HCV) infection is a critical issue for the development of novel anti-HCV drugs. To this aim, we have tried many different approaches for generating mice carrying humanized liver. Main efforts were focused on the transplantation of human hepatocytes into im...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2006.02.149
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND:We describe an observational, retrospective study that included patients who underwent a liver transplantation (LT) for hepatocellular carcinoma (HCC) in our center between 2004 and 2012. METHODS:Clinical variables were recorded for donors and recipients as diagnosis and treatment, immunosuppressive therapy...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2015.08.020
更新日期:2015-10-01 00:00:00
abstract::During the rejection process of cardiac allografts, the expression of HLA antigens increases on various graft tissues, ie, the myocardium and the interstitial structures. However, in this type of transplant there is a paucity of knowledge about HLA expression on recipient cells, such as peripheral blood mononuclear ce...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2007.07.001
更新日期:2007-09-01 00:00:00
abstract:INTRODUCTION:In this study, hemoglobin (Hb) concentrations secondary to enalapril (E) or losartan (L) therapy were evaluated with respect to renin-angiotensin system (RAS) polymorphisms in renal transplant recipients. MATERIALS AND METHODS:After determination of RAS polymorphisms [angiotensin-converting enzyme (DD, no...
journal_title:Transplantation proceedings
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.transproceed.2007.02.016
更新日期:2007-05-01 00:00:00
abstract:OBJECTIVE:The goal of this article is to present the experience of a new liver transplant team. MATERIALS AND METHODS:This review includes all patients who received a liver transplant between March 15, 2000 and March 15, 2003. RESULTS:We performed 87 transplantations on 84 patients; 39 were females and 45 were males ...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2004.06.020
更新日期:2004-07-01 00:00:00
abstract:PURPOSE:The aim was to study the effect of an antibody-mediated response on rat chronic liver rejection. METHODS:Liver transplantation was performed in rats assigned to one of the 3 treatment groups: group A, Brown Norway (BN) to BN + CsA; group B, dark Agouti (DA) to BN; and group C, DA to BN + CsA. In addition to su...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2011.03.043
更新日期:2011-06-01 00:00:00
abstract::Evaluation of research products released during activities that have received public funds should be a mandatory practice. In this study, we evaluated the research products released during the research program "Innovative Strategies to Expand Cadaveric Donor Pool for Liver Transplantation" (SITF Project), funded by th...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2008.05.017
更新日期:2008-07-01 00:00:00
abstract::Proper maintenance of immunosuppression is required to achieve long-term graft survival. The aim of this study was to evaluate the effect of change or modulation of an immunosuppressive regimen (IR) on graft survival during the posttransplant period in patients undergoing kidney transplantation. A total of 1164 patien...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2010.10.021
更新日期:2010-12-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to evaluate whether 3-dimensional computerized tomographic angiography (3D-CTA) is useful to detect transplant renal artery stenosis (TRAS). METHODS:Fourteen patients with clinically suspected TRAS underwent color Doppler ultrasonography (CDU) and 3D-CTA before renal angiography. We...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2011.12.007
更新日期:2012-04-01 00:00:00
abstract:INTRODUCTION:Current organ supply system depends on altruistic noncoercive donation, which has failed to meet the demand of organ transplantation. Providing financial incentives to donors is one of several approaches to address organ shortage. However, its feasibility is debatable as it relates to medical, ethical, and...
journal_title:Transplantation proceedings
pub_type: 杂志文章
doi:10.1016/j.transproceed.2014.06.024
更新日期:2014-07-01 00:00:00