Livers from male Sprague-Dawley rats were perfused with heparinised, unmodified isogeneic rat blood (n = 6) or xenogeneic human blood. The microcirculation of these livers, as the primary manifestation of hyperacute xenogeneic rejection, was directly observed and quantified by using fluorescence videomicroscopy. Bile flow and enzyme release of the isogeneic perfused livers were in the physiological range, whereas bile flow was significantly reduced and enzyme release increased during xenogeneic perfusion. In contrast to an almost physiological acinar (90.4%) and sinusoidal (93.6%) perfusion rate in the isogeneic group, a rapid breakdown of microcirculation with an acinar perfusion index of 47.5% and a sinusoidal perfusion rate of 67.1% were found in the xenogeneic group. This direct quantification of microcirculatory parameters is a step forward towards sensitive and early characterisation of the severity of the xenogeneic rejection of the liver.
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http://dx.doi.org/10.1007/978-3-662-00818-8_25 | DOI Listing |
Clin Transplant Res
December 2024
The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea.
Foreign antigen recognition is the ability of immune cells to distinguish self from nonself, which is crucial for immune responses in both invertebrates and vertebrates. In vertebrates, T cells play a pivotal role in graft rejection by recognizing alloantigens presented by antigen-presenting cells through direct, indirect, or semidirect pathways. B cells also significantly contribute to the indirect presentation of antigens to T cells.
View Article and Find Full Text PDFTranspl Int
December 2024
Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.
Xenotransplantation of porcine organs has made remarkable progress towards clinical application. A key factor has been the generation of genetically multi-modified source pigs for xenotransplants, protected against immune rejection and coagulation dysregulation. While efficient gene editing tools and multi-cistronic expression cassettes facilitate sophisticated and complex genetic modifications with multiple gene knockouts and protective transgenes, an increasing number of independently segregating genetic units complicates the breeding of the source pigs.
View Article and Find Full Text PDFXenotransplantation
December 2024
The Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Conventional T cell-directed immunosuppression is the mainstay of standard-of-care therapy to prevent graft rejection in clinical organ transplantation. However, it remains ineffective in preventing experimental and clinical organ xenograft rejection. Here, we explored the impact of allogeneic versus xenogeneic antigen stimulation on human T cell responses and gene profile.
View Article and Find Full Text PDFFront Transplant
November 2024
Columbia Center of Translational Immunology, Columbia University, New York, NY, United States.
Background: Despite advances in immunosuppressive therapies, chronic rejection and immunosuppression-related complications remain significant challenges in transplantation. Developing transplantation tolerance through thymus transplantation may offer a solution. This paper details our technique for procuring and transplanting porcine vascularized thymic lobes (VTL), which can be utilized to study and research allogeneic and xenogeneic transplantation models in large animals.
View Article and Find Full Text PDFSci Rep
November 2024
Department of Rheumatology and immunology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
To develop a clinical imaging method for monitoring macrophage migration to the defect site after implantation of various stem cells and evaluating immune responses in the context of knee arthritis, T2 mapping was correlated with CD68-positive cell densities in defects and the bone marrow. This study, which was approved by the Institutional Animal Care and Use Committee, used 32 New Zealand white rabbits preloaded with ultrasmall superparamagnetic iron oxide particles (USPIOs). They were divided into groups that received different stem cell implants after osteochondral defect induction.
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