<< Back to the abstract archive
Improved compliance via loco-regional immunosuppression induces long-term survival in Vascularized Composite Allotransplantation.
Jignesh V. Unadkat MD, MRCS, Jonas Schnider MD, Kacey Marra PhD, Angus Thomson PhD, Alexander Spiess, MD.
Dept of Plastic Surgery, University of Pittsburgh Medical Center
2013-03-14
Presenter: Jignesh Unadkat
Affidavit:
This is 100% original work by Jignesh Unadkat
Director Name: Joseph E. Losee
Author Category: Resident Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: Hand
Background: Initial experience with vascularized composite allotransplantation (VCA) has shown medication non-compliance results in increased acute rejection episodes and ultimately poor long-term outcomes. Delivering immunosuppression to sites of allorecogition and T-cell activation without daily systemic immunosuppression would lead to improved compliance and overall allograft survival without systemic side-effects.
Hypothesis: Fk506 encapsulated microspheres implanted subcutaneously will release thearapeutic Fk506 to maintain VCA without daily Fk506 administration.
Methods: Fk506 was encapsulated in PLGA/PLA microspheres and incorporated into 5mm PLGA discs. Brown-Norway(BN) to Lewis(Lew) functional orthotopic hind-limb transplants were performed. Group1: Systemic Fk (daily Fk506 i.p. for 21days). Group2: 1 Fk disc in allograft. Group3: 1 Fk disc in contralateral naïve untransplanted leg. End-point 150 days survival or grade3 rejection. Blood FK levels measured at regular intervals. At end-point, blood and allograft tissue Fk levels measured.
Results: There were therapeutic blood Fk levels between 5-15ng/ml for 20, 150, 150 days in group1, 2 and 3 respectively. Allograft survival was 40(+/- 5.1), 150, 150 days in groups1, 2 and 3 respectively. There were significantly increased Fk506 levels in regional groin lymph nodes compared to blood in groups 2 and 3.
Conclusion: Implantation of one Fk disc leads to sustained Fk506 levels and prevents rejection in VCA without need for daily systemic administration. This strategy would improve compliance following VCA and induce long-term allograft survival.
