a-standardized-porcine-kidney-auto-transplant-protocol-for-studying

A Standardized Porcine Kidney Auto-transplant Protocol for Studying Delayed Graft Function

Delayed graft function (DGF) is commonly defined as the need for dialysis within 7 days after kidney transplantation; however, current definitions often ...

Duke University

Reply from the authors: Future considerations for adeno-associated viral gene therapy in ex vivo lung perfusion.

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. Subnormothermic machine perfusion (SNMP) has the potential to combine the advantages of both approaches but has undergone limited investigation. Therefore, the present study sought to determine the suitability of SNMP for extended kidney preservation.

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

The clinical success of liver transplantation has led to increased demand, requiring further expansion of the donor pool. Therapeutic interventions to optimize organs from donation after circulatory death (DCD) have significant potential to mitigate the organ shortage. Dysfunction in DCD liver grafts is mediated by microvascular thrombosis during the warm ischemic period, and strategies that reduce this thrombotic burden may improve graft function. We hypothesized that the administration of the fibrinolytic enzyme plasmin to the donor organ during the cold storage period would reduce the thrombotic burden and improve DCD liver graft function.

Optimizing DCD Liver Grafts With Prolonged Warm Ischemic Time Using Stabilized Plasmin in a Static Cold Storage Orthotopic Rat Liver Transplant Model.

Ex-vivo lung perfusion (EVLP) has emerged as a transformative technique in lung transplantation, offering a solution for evaluating and rehabilitating donor lungs that would otherwise be deemed unsuitable. This review article examines the significant advancements in EVLP technology and its application in clinical practice. We discuss the criteria for selection and rehabilitation of donor lungs, emphasizing the use of EVLP for lungs with compromised function due to factors like prolonged ischemic time and donor smoking history. Further, we elaborate on the technological advancements that have improved the functional assessment of lungs, including the development of more sophisticated perfusion solutions and the integration of artificial intelligence for real-time assessment. Additionally, we discuss the future prospects of EVLP, focusing on potential innovations in perfusion solutions, the integration of regenerative medicine and gene therapy to improve allograft quality. Through this comprehensive review, we aim to provide a clear understanding of the current status of EVLP and its promising future directions, ultimately contributing to improved outcomes in lung transplantation.

 lung perfusion: recent advancements and future directions.

Acute cellular rejection is a key contributor to chronic lung allograft dysfunction following transplantation; while treatable, traditional immunosuppressive therapies are associated with significant side effects. Gene therapy offers an approach to modulate recipient immune responses while minimizing the toxicity of conventional immunosuppressive therapy. In this study, we evaluated adenoassociated virus (AAV)-mediated programmed death-ligand (PD-L)1 overexpression, an inhibitory ligand of T cells, in a rat single-lung transplant model. Allogeneic Brown Norway lungs were transplanted into Fischer F344 recipients and assigned to 3 groups: (1) AAV9-PD-L1 via the bronchus during static cold storage, (2) no-virus control, or (3) AAV9-luciferase control. All animals received cytotoxic T lymphocyte-associated protein 4 immunoglobulin on postoperative day (POD)1, and killed on POD14. Rejection was evaluated by a blinded lung transplant pathologist, and PD-L1 expression and CD8 T cell infiltration assessed via immunohistochemistry. By POD14, the AAV9-PD-L1 group displayed significantly reduced rejection severity (mean score 1.40) compared to controls (mean 3.60; p=0.005). The AAV9-luciferase group exhibited comparable rejection scores to no-virus controls (mean 3.5). Immunohistochemistry confirmed exogenous PD-L1 expression, however no significant difference in CD8+ T cell count was observed between groups. These findings demonstrate that AAV-PD-L1 gene delivery can attenuate acute cellular rejection in lung transplants, offering a potential strategy to improve outcomes.

Adeno-associated virus-mediated transduction of PD-L1 in a rodent lung transplant model.

Current clinical ex vivo lung perfusion (EVLP) perfuses the pulmonary arteries (PA) but not the bronchial arteries (BA) that normally supply the upper airway. We hypothesized that the PA alone do not fully perfuse this region during EVLP, which could lead to hypoxic injury in the central airways, especially with extended preservation. In this study, we demonstrate a method for dual-route EVLP (D-EVLP) that perfuses both the PA and BA to improve lung preservation.

Article	Year
Reply from the authors: Future considerations for adeno-associated viral gene therapy in ex vivo lung perfusion. The Journal of thoracic and cardiovascular surgery\| PubMed ID: 38430103	2024
Subnormothermic Oxygenated Machine Perfusion (24 h) in DCD Kidney Transplantation. Transplantation direct\| PubMed ID: 38807861	2024
Optimizing DCD Liver Grafts With Prolonged Warm Ischemic Time Using Stabilized Plasmin in a Static Cold Storage Orthotopic Rat Liver Transplant Model. Transplantation direct\| PubMed ID: 38988689	2024
lung perfusion: recent advancements and future directions. Frontiers in immunology\| PubMed ID: 40066445	2025
Adeno-associated virus-mediated transduction of PD-L1 in a rodent lung transplant model. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons\| PubMed ID: 40449603	2025
Dual ex vivo lung perfusion via pulmonary and bronchial arteries in a porcine model. JTCVS techniques\| PubMed ID: 41112451	2025

Benjamin Hughes

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