Abstract
BackgroundChronic 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.MethodsAllogeneic 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.ResultsWe 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.ConclusionsThe 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.
Highlights
Within the past 20 years, vascularized composite allotransplantation (VCA) has emerged as a new therapeutic option for severe defects in reconstructive surgery
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
CXC ligands 9–11 deserve further research to investigate their role as chronic rejection markers
Summary
Within the past 20 years, vascularized composite allotransplantation (VCA) has emerged as a new therapeutic option for severe defects in reconstructive surgery. In this relatively young field of transplantation, acute rejection (AR) is mainly understood and can roughly be divided into cell mediated rejection and antibody mediated rejection [1]. Valid experimental models for the assessment of CR are vital to uncover underlying mechanisms behind CR with potential links for treatment and predict long-term outcome of these life-changing surgeries. Given the lack of currently available studies, there is no standardized, well-established animal model to assess CR in VCA so far. 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
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