Immune Rejection of Cartilage in a Swine Vascularized Composite Allotransplantation Model

Background

Cartilage is a crucial tissue in vascularized composite allotransplantation (VCA) and plays a pivotal role in restoring motor function, especially in joint allotransplantation. Nevertheless, our understanding of immune rejection in cartilage remains limited and contentious. This study seeks to investigate the immune rejection of cartilage in a large animal model of VCA.

Methods

Cartilage, including articular cartilage and meniscus, as well as skin, muscle and lymph node, was retrieved from a swine heterotopic VCA graft when the skin of the graft suffered from grade III-IV rejection. Histologic examination, transmission electron microscopy and immunofluorescent staining were used to investigate immune rejection.

Results

Histologic examination revealed the infiltration of inflammatory cells and tissue destruction in cartilage. Transmission electron microscopy confirmed tissue damage and necrosis in cartilage. However, cartilage exhibited milder tissue damage when compared to rejected skin and muscle. Immunofluorescent staining revealed the activation of both the innate and adaptive immune systems, accompanied by an up-regulation of cell death biomarkers, including apoptosis and pyroptosis, in the rejected cartilage.

Conclusion

Our study demonstrates that cartilage is not immunologically privileged and undergoes immune rejection concurrently with skin and muscle in the VCA graft, though with less severe inflammation and rejection.