Purpose: Transplantatation of vascularized skin allografts such as the groin flaps could have important clinical applications for wound coverage. The need for life long immunosuppression is precluding the routine use of skin allografts. In this study, we investigated the effect of the short 7 days protocols of immunosuppressive monotherapies and combined abTCR+CsA therapies on the extension of survival of vascularized skin allografts in the rat experimental model
Methods: Thirty allotransplantations across strong MHC barrier were performed between ACI (RT1a) donors and LEW (RT1l) recipients in 6 groups. Isograft (n=6) and allograft rejection controls (n=6) received no treatment. Treated groups received either rat abTCR (n=6) or CsA (n=6) monotherapies or combination of abTCR+CsA (n=6) for 7 days only. The survival of the flaps was evaluated by the clinical and histopathological examination. The efficacy of immunosuppressive treatment and the level of donor specific chimerism in the peripheral blood of recipients were determined by flow cytometry (FC).
Results: Indefinite flap survival was observed in isograft controls. Allograft controls were rejected between 5-7 days posttransplant. The monotherapy of abTCR and CsA, extended survival up to 11.6±3.0 and 15.8±2.3 respectively. The combined abTCR+CsA therapy prolonged vascularized skin allograft survival up to 58.5±28.1 (p<00.5) days after transplantation. FC analysis revealed high efficacy of the immunosuppressive treatment and stable donor specific chimerism in the peripheral blood of long-term survivors, which ranged between 2-4%.
Conclusions: In this study, significant extension of the vascularized skin allografts survival across strong MHC barrier was achieved under combined abTCR+CsA protocols. This was associated with the presence of multi-lineage chimerism in the peripheral blood of tolerated recipients.