A5047542433- Organ Transplantation Techniques and Outcomes
- Liver Disease and Transplantation
- Renal Transplantation Outcomes and Treatments
- Xenotransplantation and immune response
- Pancreatic function and diabetes
- Organ Donation and Transplantation
- Liver Disease Diagnosis and Treatment
- Diabetes and associated disorders
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- Hepatocellular Carcinoma Treatment and Prognosis
- Animal Genetics and Reproduction
- Transplantation: Methods and Outcomes
- Gallbladder and Bile Duct Disorders
- Toxin Mechanisms and Immunotoxins
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cannabis and Cannabinoid Research
- RNA Interference and Gene Delivery
- Cytomegalovirus and herpesvirus research
- Immunotherapy and Immune Responses
- Pregnancy and Medication Impact
- Pediatric Hepatobiliary Diseases and Treatments
- Liver physiology and pathology
- Hepatitis C virus research
- Pancreatitis Pathology and Treatment
Beth Israel Deaconess Medical Center
2021-2025
Harvard University
2021-2024
Hadassah Medical Center
2021-2024
University of Alabama at Birmingham
2013-2022
Xenotran (United States)
2018-2022
University Gastroenterology
2022
Health Resources and Services Administration
2018
NHS Blood and Transplant
1999-2017
Society of Surgical Oncology
2015-2016
Association for Surgical Education
2015-2016
Antipig antibodies are a barrier to clinical xenotransplantation. We evaluated antibody binding of waitlisted renal transplant patients 3 glycan knockout (KO) pig cells and class I swine leukocyte antigens (SLA).Peripheral blood mononuclear from SLA identical wild type (WT), α1, 3-galactosyltransferase (GGTA1) KO, GGTA1/ cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) CMAH /b1,4 N-acetylgalactosaminyl transferase (B4GalNT2) KO pigs were screened for human using flow...
To compare conventional low-temperature storage of transplant donor livers [static cold (SCS)] with the organs at physiological body temperature [normothermic machine perfusion (NMP)].
The immunosuppressive activity of RS-61443, a semisynthetic derivative mycophenolic acid, was examined in 33 canine renal allografts. Initial studies established that triple therapy consisting 20 mg/kg RS-61443 combination with 5 cyclosporine and 0.1 methylprednisolone the optimal to prevent graft rejection. median survival time 8.1±1.2 days dogs without treatment (n=5), 8.5±1.7 control group (CsA mg/kg, MP mg/kg; n=6), 36.0±9.6 monotherapy (40 n=6); 122.4±38.75 (n=16). Graft prolongation...
Ischemia/reperfusion (IR) injury in transplanted livers contributes to organ dysfunction and failure is characterized part by loss of NO bioavailability. Inhalation nontoxic at high concentrations (80 ppm) inhibits IR extrapulmonary tissues. In this prospective, blinded, placebo-controlled study, we evaluated the hypothesis that administration inhaled (iNO; 80 patients undergoing orthotopic liver transplantation hepatic injury, resulting improved function. Patients were randomized receive...
Human intestinal macrophages contribute to tissue homeostasis in noninflamed mucosa through profound down-regulation of pro-inflammatory cytokine release. Here, we show that this extends Toll-like receptor (TLR)-induced release, as expressed TLR3-TLR9 but did not release cytokines response TLR-specific ligands. Likely contributing unique functional profile, markedly down-regulated adapter proteins MyD88 and Toll interleukin 1 domain-containing adapter-inducing interferon beta, which together...
Background: Patients infected with hepatitis C virus (HCV) frequently develop renal failure after liver transplantation. Objective: To describe histologic characteristics and concomitant clinical features in HCV-infected patients end-stage cirrhosis. Design: Case series. Setting: Single-center transplant program the United States. Patients: 30 who received transplants for HCV-induced Intervention: Kidney biopsy during engraftment. Measurements: Clinical data laboratory tests of function...
Xenotransplantation using pig organs could end the donor organ shortage for transplantation, but humans have xenoreactive antibodies that cause early graft rejection. Genome editing can eliminate xenoantigens in pigs to minimize impact of these xenoantibodies. Here we determine whether an improved cross-match and chemical immunosuppression result prolonged kidney xenograft survival a pig-to-rhesus preclinical model.
The aims of this study were to evaluate the efficacy US Food and Drug Administration-approved drugs in genetically engineered pig-to-baboon kidney xenotransplantation compare results with those using an anti-CD40 monoclonal antibody (mAb)-based regimen.Ten life-supporting transplants carried out baboons α1,3-galactosyltransferase gene-knockout/CD46 pigs various other genetic manipulations aimed at controlling coagulation dysregulation. Eight resulted informative data. Immunosuppressive...
Abstract Triple-knockout (TKO) pigs (with added protective human transgenes) are likely to be optimal sources of organs for clinical organ xenotransplantation because many humans have minimal or no natural antibody TKO pig cells. However, Old World monkeys (OWMs) naturally-existing antibodies directed We measured anti-pig IgM/IgG binding, and complement-dependent cytotoxicity wild-type (WT), α1,3-galactosyltransferase gene-knockout (GTKO), peripheral blood mononuclear cells (PBMCs) using...
Although approximately 1 million islets exist in the adult human pancreas, current pancreas preservation and islet isolation techniques recover <50%. Presently, cadaveric donors remain sole source of pancreatic tissue for transplantation. Brain death is characterized by activation proinflammatory cytokines organ injury during reperfusion. In this study, we assessed effects brain on yields functionality. was induced male 250- to 350-g Lewis rats inflation a Fogarty catheter placed...
Objective To examine the possibility of reducing ischemia-reperfusion injury (I/R injury) to mouse liver by in vivo adenovirus-mediated gene transfer antiapoptotic human Bcl-2 gene. Summary Background Data Ischemia-reperfusion has been demonstrated a number clinically relevant diseases such as myocardial infarction, cerebrovascular disease, sepsis, peripheral vascular and organ transplantation. In this regard, apoptosis plays central role. Methods Normal C57BL/6 mice were used. An adenovirus...
Background. Day of transplant T cell depletion with anti-CD3 immunotoxin or F(Ab)2 induces stable tolerance to renal allografts in rhesus monkeys given 15-deoxyspergualin (DSG), a NF-κB inhibitor that suppresses proinflammatory cytokine (PC) production. Because PC and are involved dendritic (DC) maturation, we asked if impaired DC maturation Th2-type deviation might be related the synergistic effect DSG this novel model. Methods. Immunosuppression was initiated 4 hr before transplanting...
Abstract The lamina propria of the gastrointestinal mucosa contains largest population mononuclear phagocytes in body, yet little is known about cellular mechanisms that regulate cell recruitment to noninflamed and inflamed intestinal mucosa. Here, we show macrophages do not proliferate. We also a substantial proportion express chemokine receptors for interleukin (IL)-8 transforming growth factor-β (TGF-β), smaller expresses N-formylmethionyl-leucyl-phenylalanine C5a, but, surprisingly, they...
Clinical studies indicate that significant loss of functional islet mass occurs in the peritransplant period. Islets are injured as a result detrimental effects brain death, pancreas preservation, isolation, hypoxia, hyperglycemia, and immune-mediated events. In addition, recent demonstrated islets their exposure to blood activation intrahepatic endothelial Kupffer cells, resulting inflammation thrombosis. Activated protein C (APC) is an anticoagulant enzyme also exerts anti-inflammatory...
The urological complications of 210 patients who underwent simultaneous pancreas-kidney (SPK) transplantation over a 7-year period were reviewed.Worldwide, bladder drainage has become the accepted method exocrine after pancreas transplantation. With increasing use drainage, surgical post-transplant have shifted from intra-abdominal to complications.Two hundred ten diabetic received SPK transplants with drainage. A retrospective review was conducted analyze incidence, type, and management...
A major challenge in clinical transplantation today is to design a practical and effective protocol for tolerance induction compatible with cadaver organ transplantation. preclinical rhesus monkey kidney allograft model using immediate peritransplant anti-CD3 immunotoxin (anti-CD3-IT) donor bone marrow (DBM) shown here induce operational prolonged graft survival the absence of chronic immunosuppressive drugs. Bone harvested from was depleted mature alloantigen-presenting cells T by removing...
This work is a 1-yr interim analysis of prospective, randomized, multicenter trial evaluating the effect corticosteroid-free immunosuppression on hepatitis C virus-positive (HCV(+)) liver transplant recipients following transplantation (LT). Patients received tacrolimus and corticosteroids (Arm 1; n = 80); tacrolimus, corticosteroids, mycophenolate mofetil (MMF) 2; 79); or daclizumab induction, MMF 3; 153). At 1 yr, 64.1%, 63.4%, 69.4% patients achieved composite primary endpoint freedom...
This randomized, prospective, multicenter trial compared the safety and efficacy of steroid-free immunosuppression (IS) to 2 standard IS regimens in patients undergoing transplantation for hepatitis C virus (HCV) infection. The outcome measures were acute cellular rejection (ACR), severe HCV recurrence, survival. randomized (1:1:2) tacrolimus (TAC) corticosteroids (arm 1; n = 77), mycophenolate mofetil (MMF), TAC, 2; 72), or MMF, daclizumab induction with no 3; 146). In all, 295 RNA-positive...
Over 130 000 patients in the United States alone need a lifesaving organ transplant. Genetically modified porcine organs could resolve donor shortage, but human xenoreactive antibodies destroy pig cells and are major barrier to clinical application of xenotransplantation. The objective this study was determine whether waitlisted possess preformed swine leukocyte antigen (SLA) class II, homologs II HLA.Sera from people currently awaiting solid transplant were tested for IgG binding SLA...