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Strategy for Tolerance Induction in Pediatric Composite Tissue Allostransplantation
Jignesh V. Unadkat, Rami Zanoun, Greg Cooper, ALex Speis, Darren Smith, Joseph Losee
University of Pittsburgh Medical Center
2012-02-16
Presenter: Jignesh V. Unadkat
Affidavit:
All of it.
Director Name: Joseph Losee
Author Category: Chief Resident Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
How does this presentation meet the established conference educational objectives?
It will help describe new technologies in reconstructive surgery in the pediatric population.
How will your presentation be used by practicing physicians in the audience?
The protocol presented in this presentation will act as a scaffold to fuel other preclinical studies before implementing clinical human trials.
Introduction: There are immense psychological benefits of providing adequate reconstruction to a child with devastating facial injuries/congenital deformities. Current reconstructive techniques cannot replace "like for like" and are associated with donor-site morbidity. Composite tissue allotransplantation (CTA) has become a clinical reality. Our goal was to test single agent immunomodulation in inducing tolerance in pediatric rat hind-limb transplant model.
Methods: 2-3 week old male Lewis rats underwent hind limb transplantation from Brown Norway rats. Control groups include iso (Lew-Lew), Allo (BN-Lew, no immunosuppression), ALS (BN-Lew, ALS depletion day -4 before transplant), FK (BN-Lew, 21 days of 0.5mg /kg Fk506 i.p), ALS+FK (BN-Lew, ALS and 21 days of FK506). The experimental group received one dose of BN bone marrow on day of CTA in addition to ALS and FK for 21 days. Rats were followed for 100 days. Analysis include chimerism detection, mixed lymphocytic reaction, FACS for Tregs and skin graft challenge for long term survivors.
Results: One dose of ALS leads to 100% depletion of WBC in pediatric rats by day 4. There was significant long-term survival in the pediatric rats receiving donor BM along with ALS and FK. Currently we are analyzing the biopsy samples for histology, FACS and chimerism in long-term survivors. Data will be available for presentation at the meeting.
Conclusions: So far we can conclude that one dose of ALS is a potent immunodepletant in pediatric rats. Donor BM along with initial immune depletion and short term FK506 induces long-term survival in a pediatric hind-limb CTA model.
