In JoVE (2)
Other Publications (7)
- American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
- Liver International : Official Journal of the International Association for the Study of the Liver
- PloS One
- Transplantation Direct
- American Journal of Surgery
- Transplant International : Official Journal of the European Society for Organ Transplantation
- Scientific Reports
Articles by Manuel Maglione in JoVE
Murine Cervical Heart Transplantation Model Using a Modified Cuff Technique Rupert Oberhuber*1, Benno Cardini*1, Markus Kofler1, Paul Ritschl1, Robert Oellinger1, Felix Aigner1, Robert Sucher1, Stefan Schneeberger1, Johann Pratschke1, Gerald Brandacher2, Manuel Maglione1 1Center of Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, 2Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine The murine cervical heart transplantation model is well suited for immunological as well as ischemia reperfusion injury studies. We modified the procedure using a non-suture cuff technique and performed more than 1,000 successful transplants with this approach. Herein, we provide additional details of this technique to supplement the video.
Mouse Model for Pancreas Transplantation Using a Modified Cuff Technique Benno Cardini*1, Rupert Oberhuber*1, Sven R Hein1, Rebecca Eiter1, Martin Hermann2, Markus Kofler1,3, Stefan Schneeberger1, Gerald Brandacher1,4, Manuel Maglione1 1Center of Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Medical University Innsbruck, 2Department of Anesthesiology and Critical Care Medicine, Medical University Innsbruck, 4Department of Cardiac Surgery, Medical University Innsbruck, 3Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine Among abdominal solid organ transplantation, pancreatic grafts are prone to develop severe ischemia reperfusion injury-associated graft damage, leading eventually to early graft loss. This protocol describes a model of murine pancreas transplantation using a non-suture cuff technique, ideally suited for analyzing these early, deleterious damages.
Other articles by Manuel Maglione on PubMed
Donor Pretreatment with Tetrahydrobiopterin Saves Pancreatic Isografts from Ischemia Reperfusion Injury in a Mouse Model American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. | Pubmed ID: 20883557 Depletion of the nitric oxide synthase cofactor tetrahydrobiopterin (H4B) during ischemia and reperfusion is associated with severe graft pancreatitis. Since clinically feasible approaches to prevent ischemia reperfusion injury (IRI) by H4B-substitution are missing we investigated its therapeutic potential in a murine pancreas transplantation model using different treatment regimens. Grafts were subjected to 16 h cold ischemia time (CIT) and different treatment regimens: no treatment, 160 μM H4B to perfusion solution, H4B 50 mg/kg prior to reperfusion and H4B 50 mg/kg before recovery of organs. Nontransplanted animals served as controls. Recipient survival and endocrine graft function were assessed. Graft microcirculation was analyzed 2 h after reperfusion by intravital fluorescence microscopy. Parenchymal damage was assessed by histology and nitrotyrosine immunohistochemistry, H4B tissue levels by high pressure liquid chromatography (HPLC). Compared to nontransplanted controls prolonged CIT resulted in significant microcirculatory deterioration. Different efficacy according to route and timing of administration could be observed. Only donor pretreatment with H4B resulted in almost completely abrogated IRI-related damage showing graft microcirculation comparable to nontransplanted controls and restored intragraft H4B levels, resulting in significant reduction of parenchymal damage (p < 0.002) and improved survival and endocrine function (p = 0.0002 each). H4B donor pretreatment abrogates ischemia-induced parenchymal damage and represents a promising strategy to prevent IRI following pancreas transplantation.
Excellent Post-transplant Survival in Patients with Intermediate Stage Hepatocellular Carcinoma Responding to Neoadjuvant Therapy Liver International : Official Journal of the International Association for the Study of the Liver. | Pubmed ID: 26386273 Current treatment guidelines preclude liver transplantation for patients with BCLC B (intermediate stage) HCC, and expanding transplantation criteria for selected patients beyond early stage HCC remains controversial. The aim of this study was to determine stage-dependent HCC recurrence and overall survival rates in transplant recipients and the impact of response to neoadjuvant treatment on outcome.
Identification of Molecular Markers of Delayed Graft Function Based on the Regulation of Biological Ageing PloS One. | Pubmed ID: 26734715 Delayed graft function is a prevalent clinical problem in renal transplantation for which there is no objective system to predict occurrence in advance. It can result in a significant increase in the necessity for hospitalisation post-transplant and is a significant risk factor for other post-transplant complications.
Functional Capillary Density in Ischemic Conditioning: Implications for Esophageal Resection with the Gastric Conduit American Journal of Surgery. Jul, 2008 | Pubmed ID: 18367142 Ischemia may lead to leakage at the esophagogastric anastomosis after esophagectomy. The aim of this study was to investigate time dependent changes of gastric microcirculation after ischemic conditioning.
Prevention of Lethal Murine Pancreas Ischemia Reperfusion Injury is Specific for Tetrahydrobiopterin Transplant International : Official Journal of the European Society for Organ Transplantation. Oct, 2012 | Pubmed ID: 22805419 Tetrahydrobiopterin has been shown to efficiently abrogate ischemia reperfusion injury (IRI). However, it is unclear, whether its beneficial action relies on cofactor activity of one of the five known tetrahydrobiopterin-dependent reactions or on its antioxidative capacity. We therefore compared tetrahydrobiopterin with the pterin derivate tetrahydroneopterin (similar biochemical properties, but no nitric oxide synthase cofactor activity) and the antioxidants vitamin C and 5-methyltetrahydrofolate. Donor mice were pretreated with tetrahydrobiopterin, tetrahydroneopterin, vitamin C, or 5-methyltetrahydrofolate. Pancreatic grafts were subjected to 16-h cold ischemia time and implanted in syngeneic recipients. Untreated and nontransplanted animals served as controls. Following 2-h reperfusion, microcirculation was analyzed by intravital fluorescence microscopy. Graft damage was assessed by histology and nitrotyrosine immunostaining, and tetrahydrobiopterin levels were determined by HPLC. Recipient survival served as ultimate readout. Prolonged cold ischemia time resulted in microcirculatory breakdown. Only tetrahydrobiopterin pretreatment succeeded to preserve the capillary net, whereas all other compounds showed no beneficial effects. Along with increased intragraft tetrahydrobiopterin levels during recovery and implantation, only tetrahydrobiopterin pretreatment led to significant reduction of IRI-related parenchymal damage enabling recipient survival. These results show a striking superiority of tetrahydrobiopterin in preventing lethal IRI compared with related compounds and suggest nitric oxide synthases as treatment target.
Impaired Endothelial Nitric Oxide Synthase Homodimer Formation Triggers Development of Transplant Vasculopathy - Insights from a Murine Aortic Transplantation Model Scientific Reports. Nov, 2016 | Pubmed ID: 27883078 Transplant vasculopathy (TV) represents a major obstacle to long-term graft survival and correlates with severity of ischemia reperfusion injury (IRI). Donor administration of the nitric oxide synthases (NOS) co-factor tetrahydrobiopterin has been shown to prevent IRI. Herein, we analysed whether tetrahydrobiopterin is also involved in TV development. Using a fully allogeneic mismatched (BALB/c to C57BL/6) murine aortic transplantation model grafts subjected to long cold ischemia time developed severe TV with intimal hyperplasia (α-smooth muscle actin positive cells in the neointima) and endothelial activation (increased P-selectin expression). Donor pretreatment with tetrahydrobiopterin significantly minimised these changes resulting in only marginal TV development. Severe TV observed in the non-treated group was associated with increased protein oxidation and increased occurrence of endothelial NOS monomers in the aortic grafts already during graft procurement. Tetrahydrobiopterin supplementation of the donor prevented all these early oxidative changes in the graft. Non-treated allogeneic grafts without cold ischemia time and syngeneic grafts did not develop any TV. We identified early protein oxidation and impaired endothelial NOS homodimer formation as plausible mechanistic explanation for the crucial role of IRI in triggering TV in transplanted aortic grafts. Therefore, targeting endothelial NOS in the donor represents a promising strategy to minimise TV.