Plastic Surgery Research Council
PSRC Main Site Meeting Home Accreditation Local Area Attractions Past & Future Meetings

Back to 2017 Program


Intra-graft injection of tacrolimus may modulate local immune response promoting long-term acceptance of VCA in a modified Brown Norway-to-Lewis transplantation model.
Radu Olariu1, Adriano Taddeo2, Franck Leclère1, Mihai A. Constantinescu1, Esther Voegelin1.
1Clinic of Plastic and Hand Surgery, Inselspital, Bern University Hospital, University of Bern, Switzerland; 2Department of Clinical Research, University of Bern, Bern, Switzerland

Introduction: Side effects associated with systemic immunosuppression remain a pace-limiting obstacle to widespread adoption of vascularized composite allotransplantation (VCA). Unlike most solid organ transplantations, VCA offer unique possibilities to monitor rejection and deliver immunosuppressive drugs directly into the graft, in particular into the skin, the most immunogenic components in the VCA. We hypothesized that local delivered immunosuppressant may modulate the regional immune response and inflammatory milieu influencing the rejection process.
Material and Methods: In order to analyze the therapeutic and immunomodulatory efficacy of locally delivered immunosuppression we performed a modified Brow Norway-to-Lewis rat hind-limb transplantation model with inclusion of the vascularized inguinal lymphatic tissue in the graft. The day after the operation the rats were treated with a single sub-cutaneous injection of 7 mg tacrolimus into the transplanted limb.
Results: In order to analyze the therapeutic and immunomodulatory efficacy of locally delivered immunosuppression we performed a modified Brow Norway-to-Lewis rat hind-limb transplantation model with inclusion of the vascularized inguinal lymphatic tissue in the graft. The day after the operation the rats were treated with a single sub-cutaneous injection of 7 mg tacrolimus into the transplanted limb. The treatment significantly prolonged graft survival as compared to untreated animals (n=12 median survival 152.5 days; n=9 median survival 11 days, respectively). Interestingly, 50% of the rats survived for an average of 70.5 days and the other 50% remained rejection-free for more that 200 days without any further intervention. This dichotomy was associated neither with differential levels of systemic or intra-graft tacrolimus, nor with induction of tolerance (analyzed by mixed lymphocyte reaction, or secondary challenge with skin-graft). Notably, a better preservation of circulating Treg after therapy and a long-lasting macro-chimerism were observed in the long-term surviving rats.
Conclusions: Our data show that locally administered immunosuppression may induce an immunomodulatory milieu within the graft able to promote the long-term acceptance of VCA in a modified lymph node-including model of allotransplantation. This study suggests that the therapeutic modulation of the regional immunity may influence the outcome of VCA and underline that tissue-specific immunoresponse warrants further investigation in VCA.


Back to 2017 Program


Duke Medical Center Brightleaf Square Habitat Bike Ride Durham Farmers Market