1. A chronic rejection model and potential biomarkers for vascularized composite allotransplantation
- Author
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Puscz, Flemming, Dadras, Mehran, Dermietzel, Alexander, Jacobsen, Frank, Lehnhardt, Marcus, Behr, Björn, Hirsch, Tobias, and Kueckelhaus, Maximilian
- Subjects
Graft Rejection ,Physiology ,Microarrays ,Biochemistry ,Major Histocompatibility Complex ,Contractile Proteins ,Immune Physiology ,Medicine and Health Sciences ,Musculoskeletal System ,Skin ,Vascularized Composite Allotransplantation ,Innate Immune System ,Arteries ,Hindlimb ,Bioassays and Physiological Analysis ,Cytokines ,Medicine ,Anatomy ,Research Article ,Science ,Immunology ,Motor Proteins ,Muscle Tissue ,Actin Motors ,Myosins ,Research and Analysis Methods ,Transplantation Immunology ,Molecular Motors ,Animals ,ddc:610 ,Transplant Rejection ,Biology and Life Sciences ,Proteins ,Cell Biology ,Molecular Development ,Femoral Arteries ,Fibrosis ,Rats ,Cytoskeletal Proteins ,Disease Models, Animal ,Biological Tissue ,Gene Expression Regulation ,Immune System ,Body Limbs ,Chronic Disease ,Cardiovascular Anatomy ,Blood Vessels ,Clinical Immunology ,Clinical Medicine ,Biomarkers ,Developmental Biology - Abstract
\(\bf Background\) Chronic rejection remains the Achilles heel in vascularized composite allotransplantation. Animal models to specifically study chronic rejection in vascularized composite allotransplantation do not exist so far. However, there are established rat models to study chronic rejection in solid organ transplantation such as allogeneic transplantation between the rat strains Lewis and Fischer344. Thus, we initiated this study to investigate the applicability of hindlimb transplantation between these strains to imitate chronic rejection in vascularized composite allotransplantation and identify potential markers. \(\bf Methods\) Allogeneic hindlimb transplantation were performed between Lewis (recipient) and Fischer344 (donor) rats with either constant immunosuppression or a high dose immunosuppressive bolus only in case of acute skin rejections. Histology, immunohistochemistry, microarray and qPCR analysis were used to detect changes in skin and muscle at postoperative day 100. \(\bf Results\) We were able to demonstrate significant intimal proliferation, infiltration of CD68 and CD4 positive cells, up-regulation of inflammatory cytokines and initiation of muscular fibrosis in the chronic rejection group. Microarray analysis and subsequent qPCR identified CXC ligands 9–11 as potential markers of chronic rejection. \(\bf Conclusions\) The Fischer344 to Lewis hindlimb transplantation model may represent a new option to study chronic rejection in vascularized composite allotransplantation in an experimental setting. CXC ligands 9–11 deserve further research to investigate their role as chronic rejection markers.
- Published
- 2020