CD154 blockade effectively controls antibody-mediated rejection in highly sensitized nonhuman primate kidney transplant recipients.

Current desensitization and maintenance immunosuppression regimens for kidney transplantation in sensitized individuals show limited ability to control the posttransplant humoral response, resulting in high rates of antibody-mediated rejection (ABMR) and graft failure. Here, we showed that anti-CD154 monoclonal antibody (mAb)-based immunosuppression more effectively controlled allograft rejection and humoral rebound in a highly sensitized nonhuman primate kidney transplantation model compared with tacrolimus-based standard-of-care (SOC) immunosuppression. Desensitization with an anti-CD154 mAb (5C8) and a proteasome inhibitor led to decreased donor-specific antibodies (DSAs) and disruption of lymph node germinal centers with reduction of proliferating, memory, and class-switched B cells as well as T follicular helper cells.

Immunoproteasome inhibition reduces donor specific antibody production and cardiac allograft vasculopathy in a mouse heart transplantation model.

Objective: Cardiac Allograft Vasculopathy (CAV), a process of vascular damage accelerated by antibody-mediated rejection (AMR), is one of the leading causes of cardiac transplant failure. Proteasome inhibitors (PIs) are utilized to treat AMR, however PI-associated toxicity limits their therapeutic utility. Novel immunoproteasome inhibitors (IPIs) have higher specificity for immune cells and have not been investigated for AMR in cardiac transplant patients.

Transforming the logistics of liver transplantation with normothermic machine perfusion: Clinical impact versus cost.

Normothermic machine perfusion (NMP) facilitates utilization of marginal liver allografts. It remains unknown whether clinical benefits offset additional costs in the real-world setting. We performed a comparison of outcomes and hospitalization costs for donor livers preserved by NMP versus static cold storage (SCS) at a high-volume center.

Animal Models Within Surgical Simulation: A Novel Approach to the 3 Rs.

Introduction: Development of technical skills is a vital component of surgical residency. The use of animal tissues for operative simulation leads to both the loss of animal life and financial costs for the institution. We hypothesized that maximizing tissue use from investigational large animal models after euthanasia could reduce loss of animal life and institutional costs by replacing commercially purchased tissues.

Acoustofluidic-based therapeutic apheresis system.

Therapeutic apheresis aims to selectively remove pathogenic substances, such as antibodies that trigger various symptoms and diseases. Unfortunately, current apheresis devices cannot handle small blood volumes in infants or small animals, hindering the testing of animal model advancements. This limitation restricts our ability to provide treatment options for particularly susceptible infants and children with limited therapeutic alternatives.

Allosensitisation in NHP results in cross-reactive anti-SLA antibodies not detected by a lymphocyte-based flow cytometry crossmatch.

Xenotransplantation is a potential option for individuals for whom an acceptable human allograft is unavailable. Individuals with broadly reactive HLA antibodies due to prior exposure to foreign HLA are potential candidates for a clinical xenotransplant trial. It remains controversial if allosensitisation results in the development of cross-reactive antibodies against SLA.

Belatacept and carfilzomib-based treatment for antibody-mediated rejection in a sensitized nonhuman primate kidney transplantation model.

Introduction: One-third of HLA-incompatible kidney transplant recipients experience antibody mediated rejection (AMR) with limited treatment options. This study describes a novel treatment strategy for AMR consisting of proteasome inhibition and costimulation blockade with or without complement inhibition in a nonhuman primate model of kidney transplantation.

Methods: All rhesus macaques in the present study were sensitized to maximally MHC-mismatched donors by two sequential skin transplants prior to kidney transplant from the same donor.

Altering electronic structure of nickel foam supported CoNi-based oxide through Al ions modulation for efficient oxygen evolution reaction.

Developing highly active and durable non-precious metal-based electrocatalysts for the oxygen evolution reaction (OER) is crucial in achieving efficient energy conversion. Herein, we reported a CoNiAlO/NF nanofilament that exhibits higher OER activity than previously reported IrO-based catalysts in alkaline solution. The as-synthesized CoNiAlO/NF catalyst demonstrates a low overpotential of 230 mV at a current density of 100 mA cm, indicating its high catalytic efficiency.

Prolonged xenokidney graft survival in sensitized NHP recipients by expression of multiple human transgenes in a triple knockout pig.

Genetic modification of porcine donors, combined with optimized immunosuppression, has been shown to improve outcomes of experimental xenotransplant. However, little is known about outcomes in sensitized recipients, a population that could potentially benefit the most from the clinical implementation of xenotransplantation. Here, five highly allosensitized rhesus macaques received a porcine kidney from (α1,3-galactosyltransferase) knockout pigs expressing the human transgene (1KO.

Subnormothermic Oxygenated Machine Perfusion (24 h) in DCD Kidney Transplantation.

Background: Ex vivo kidney perfusion is an evolving platform that demonstrates promise in preserving and rehabilitating the kidney grafts. Despite this, there is little consensus on the optimal perfusion conditions. Hypothermic perfusion offers limited functional assessment, whereas normothermic perfusion requires a more complex mechanical system and perfusate.

Contemporary trends and outcomes after liver transplantation and resection for intrahepatic cholangiocarcinoma.

Background: Liver transplantation (LT) has been shown to be superior to resection in highly selected patients with perihilar cholangiocarcinoma (CCA), yet has traditionally been contraindicated for intrahepatic CCA (iCCA). Herein, we aimed to examine contemporary trends and outcomes for surgical resection and LT for iCCA.

Methods: The National Cancer Database was queried for patients presenting with stage I-III iCCA between 2010 and 2018 who underwent resection or LT.

The impact of IdeS (imlifidase) on allo-specific, xeno-reactive, and protective antibodies in a sensitized rhesus macaque model.

Background: Highly sensitized patients face many barriers to kidney transplantation, including higher rates of antibody-mediated rejection after HLA-incompatible transplant. IdeS, an endopeptidase that cleaves IgG nonspecifically, has been trialed as desensitization prior to kidney transplant, and successfully cleaves donor-specific antibody (DSA), albeit with rebound.

Methods: IdeS was generated and tested (2 mg/kg, IV) in two naïve and four allosensitized nonhuman primates (NHP).

Design and testing of a humanized porcine donor for xenotransplantation.

Recent human decedent model studies and compassionate xenograft use have explored the promise of porcine organs for human transplantation. To proceed to human studies, a clinically ready porcine donor must be engineered and its xenograft successfully tested in nonhuman primates. Here we describe the design, creation and long-term life-supporting function of kidney grafts from a genetically engineered porcine donor transplanted into a cynomolgus monkey model.

The anti-CD40L monoclonal antibody AT-1501 promotes islet and kidney allograft survival and function in nonhuman primates.

Prior studies of anti-CD40 ligand (CD40L)-based immunosuppression demonstrated effective prevention of islet and kidney allograft rejection in nonhuman primate models; however, clinical development was halted because of thromboembolic complications. An anti-CD40L-specific monoclonal antibody, AT-1501 (Tegoprubart), was engineered to minimize risk of thromboembolic complications by reducing binding to Fcγ receptors expressed on platelets while preserving binding to CD40L. AT-1501 was tested in both a cynomolgus macaque model of intrahepatic islet allotransplantation and a rhesus macaque model of kidney allotransplantation.

A multivariate dataset on profiling personality traits, social and cognitive determinants of omani students' entrepreneurial intention.

This data article collects and validates a multivariate dataset on personality traits, social, and cognitive predictors of the entrepreneurial intention of 276 students of three Omani universities. Administering a validated questionnaire, a pilot study was conducted by taking a sample of 60 responses to ensure the robustness of the survey scales. Following the pilot study, the final data were collected from 276 UG and PG level students in February 2021, which were first cleaned for missing, unengaged, and outlier responses before going ahead with statistical analyses.

AAV9-mediated gene delivery to liver grafts during static cold storage in a rat liver transplant model.

Introduction: Recombinant adeno-associated virus (rAAV) is a novel strategy used clinically for gene delivery, but has not been characterized in the context of organ transplantation. We sought to determine the efficacy of rAAV-mediated gene delivery during static cold storage (SCS) prior to liver transplantation.

Methods: A triple-plasmid transfection protocol was used to produce rAAV subtype-9 vectors containing firefly luciferase genomes in HEK293 cells.

Desensitization and belatacept-based maintenance therapy in pregnancy-sensitized monkeys receiving a kidney transplant.

Among sensitized patients awaiting a transplant, females are disproportionately represented, partly because of pregnancy-induced sensitization. Using female NHPs sensitized by pregnancy alone, we examined the efficacy of costimulation blockade and proteasome inhibition for desensitization. Three animals received no desensitization (control), and seven animals received weekly carfilzomib (27 mg/m) and belatacept (20 mg/kg) before kidney transplantation.

Xenorecognition and costimulation of porcine endothelium-derived extracellular vesicles in initiating human porcine-specific T cell immune responses.

Porcine vascular endothelial cells (PECs) form a mechanistic centerpiece of xenograft rejection. Here, we determined that resting PECs release swine leukocyte antigen class I (SLA-I) but not swine leukocyte antigen class-II DR (SLA-DR) expressing extracellular vesicles (EVs) and investigated whether these EVs proficiently initiate xenoreactive T cell responses via direct xenorecognition and costimulation. Human T cells acquired SLA-I EVs with or without direct contact to PECs, and these EVs colocalized with T cell receptors.

Attitudes of patients with renal disease on xenotransplantation: A systematic review.

Background: Recent years have seen major advancements in xenotransplantation: the first pig-to-human heart transplant, the development of a brain-dead recipient model for kidney xenotransplantation, and the registration of the first xenokidney clinical trial. The attitudes of patients with kidney disease or transplants on xenotransplantation and an assessment of their reservations and considerations regarding the technology are crucial to successful clinical translation and eventual widespread implementation.

Methods: This systematic review was registered through PROSPERO (CRD42022344581) prior to initiation of the study and reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines.

Incidence of Postreperfusion Hyperfibrinolysis in Liver Transplantation by Donor Type and Observed Treatment Strategies.

Background: Hyperfibrinolysis is a possible complication during liver transplantation, particularly immediately after reperfusion.

Methods: We performed a retrospective study to examine the incidence, treatment, and resolution of postreperfusion hyperfibrinolysis in patients undergoing liver transplantation at Duke University Hospital from 2015 to 2020.

Results: Out of 535 patients undergoing liver transplantation, 21 or 3.

Complement-targeting therapeutics for ischemia-reperfusion injury in transplantation and the potential for delivery.

Organ shortages and an expanding waitlist have led to increased utilization of marginal organs. All donor organs are subject to varying degrees of IRI during the transplant process. Extended criteria organs, including those from older donors and organs donated after circulatory death are especially vulnerable to ischemia-reperfusion injury (IRI).