A5071625680- Xenotransplantation and immune response
- Organ Transplantation Techniques and Outcomes
- Virus-based gene therapy research
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- COVID-19 Clinical Research Studies
- Long-Term Effects of COVID-19
- Blood transfusion and management
- Cardiac Ischemia and Reperfusion
- 3D Printing in Biomedical Research
- Retinal and Optic Conditions
- Transplantation: Methods and Outcomes
- Organ and Tissue Transplantation Research
- Cardiac Arrhythmias and Treatments
- Mesenchymal stem cell research
- Tissue Engineering and Regenerative Medicine
- Atrial Fibrillation Management and Outcomes
- Cardiac electrophysiology and arrhythmias
- Renal Transplantation Outcomes and Treatments
- SARS-CoV-2 and COVID-19 Research
- CRISPR and Genetic Engineering
- Pancreatic function and diabetes
- Blood properties and coagulation
- Renal function and acid-base balance
- Pluripotent Stem Cells Research
University of Bern
2020-2024
Abstract Xenotransplantation using pig organs has achieved survival times up to 195 days in orthotopic heart transplantation into baboons. Here we demonstrate that addition an improved immunosuppressive regimen, non-ischaemic preservation with continuous perfusion and control of post-transplantation growth the transplant, prevention transmission porcine cytomegalovirus (PCMV) plays important role achieving long times. For first time PCMV xenotransplantation was associated a reduced...
Abstract Background Successful preclinical transplantations of porcine hearts into baboon recipients are required before commencing clinical trials. Despite years research, over half the orthotopic cardiac xenografts were lost during first 48 hours after transplantation, primarily caused by perioperative xenograft dysfunction (PCXD). To decrease rate PCXD, we adopted a preservation technique cold non‐ischemic perfusion for our ongoing pig‐to‐baboon xenotransplantation project. Methods...
The blockade of the CD40/CD40L immune checkpoint is considered essential for cardiac xenotransplantation. However, it still unclear which single antibody directed against CD40 or CD40L (CD154), combination antibodies, better at preventing organ rejection. For example, high doses administered in previous experiments might not be feasible treatment humans, while thrombotic side effects were described first-generation anti-CD40L antibodies. To address these issues, we conducted six orthotopic...
Endothelial dysfunction is an early event of vascular injury defined by a proinflammatory and procoagulant endothelial cell (EC) phenotype. Although glycocalyx disruption associated with damage, how various inflammatory stimuli affect the whether arterial venous cells respond differently unknown. Using 3D round-channel microfluidic system we investigated glycocalyx, particularly heparan sulfate (HS), on porcine ECs. Heparan (HS)/glycocalyx expression was observed already under static...
Xenotransplantation is a promising approach to reduce organ shortage, while genetic modification of donor pigs has significantly decreased the immunogenic burden xenotransplants, rejection still hurdle. Genetically modified pig organs are used in xenotransplantation research, and first clinical pig-to-human heart transplantation was performed 2022. However, impact not been investigated on cellular level yet. Endothelial cells (EC) their sugar-rich surface known as glycocalyx barrier...
Xenotransplantation using pig organs has achieved survival times of more than 195 days in orthotopic heart transplantation into baboons. Here we demonstrate that addition to an improved immunosuppressive regimen, non-ischaemic preservation with continuous perfusion and control post-transplantation growth the transplant, prevention transmission porcine cytomegalovirus (PCMV) plays important role achieving long times. For first time PCMV xenotransplantation was associated a reduced transplant...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with systemic inflammation and vascular injury, which contribute to the development of (ARDS) mortality COVID-19 infection. Moreover, multiorgan complications due persistent endothelial dysfunction have suspected as cause post-acute sequelae SARS-CoV-2 Therefore, elucidation inflammatory effect will increase our understanding how cells (ECs) short- long-term consequences Here, we investigated...
The lymphatic system plays an active role in modulating inflammation autoimmune diseases and organ rejection. In this work, we hypothesized that the transfer of donor lymph node (LN) might be used to promote lymphangiogenesis influence rejection vascularized composite allotransplantation (VCA).Hindlimb transplantations were performed which (1) recipient rats received VCA containing LN (D:LN+), (2) depleted all (D:LN-), (3) D:LN+ followed by inhibition using a vascular endothelial growth...
<title>Abstract</title> Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with systemic inflammation and vascular injury, which contribute to the development of (ARDS) mortality COVID-19 infection. Moreover, multiorgan complications due persistent endothelial dysfunction have suspected as cause post-acute sequelae SARS-CoV-2 Therefore, elucidation inflammatory effect will increase our understanding how cells (EC) short- long-term consequences Here, we...
Abstract Background Cardiac microvascular obstruction (MVO) is a frequent injury of the myocardial microcirculation after successful recanalisation occluded coronary artery in infarction. At least part, MVO caused by embolised microthrombi less than 200 µm diameter [1]. leads to hypoperfusion myocardium and negatively affects patient outcomes. However, there no effective treatment for [2, 3]. Thrombolytic drugs are promising approach, but they difficult deliver area, an increased risk...
Introduction: Organs from genetically modified pigs have been successfully used in pre-clinical xenotransplantation research, but rejection is still a major hurdle to xenograft survival. Endothelial cells (ECs) and their sulfated, sugar-rich surface known as the glycocalyx are first barrier encountered by recipient’s immune system, making them target for rejection. While shedding occur different inflammatory conditions during transplant rejection, it currently not well how of ECs changes...
Genetic modification to the donor pig candidates for organ xenotransplantation currently serves as most promising option bypass great interspecies immunological barriers that lead xenograft rejection. However, selecting optimum combination of genetic modification, which comprises removal xenoreactive porcine antigens and expression xenoprotective genes, remains a challenge. Previously we have established 3D endothelial cell culture grown under pulsatileflow shear stress using microfluidic...
Abstract Genetically tailored pigs to eliminate human immune rejection of xenografts is one promising solution the global donor organ shortage. The development xenograft transplantation has however been hampered by incomplete understanding its and inability test this in a setting. Here we use an ex vivo perfusion system with whole blood assess initial activation within endothelium at single cell transcriptome level. Renal injury, complement deposition, coagulation lymphocyte influx are all...