THE REVERSED PARADIGM OF CHIMERISM INDUCTION: DONOR CONDITIONING WITH RECIPIENT-DERIVED BONE MARROW CELLS AS A NOVEL APPROACH FOR TOLERANCE INDUCTION IN VASCULARIZED COMPOSITE ALLOTRANSPLANTATION

Purpose: To test a new approach of donor conditioning with recipient bone marrow cells (BMC) to induce tolerance in vascularized composite allograft (VCA) transplantation. Methods: Lewis rats' (recipients) BMC were stained with PKH-26. The ACI rats (donors) were conditioned with 80 x 10(6) Lewis BMC, 24 or 72 hours before VCA (groin flap) transplantation. Forty-eight VCA were performed between ACI donors and Lewis recipients. In groups I and II, donors were preconditioned (24 and 72 hours before transplantation, respectively), and recipients received 7-day anti-alpha beta-TCR/cyclosporine-A post-transplantation. In groups III and IV, donors were preconditioned (24 and 72 hours before transplantation, respectively), and recipients received no systemic immunosuppression. In group V, recipients received 7-day anti-alpha beta-TCR/cyclosporine-A post-transplantation. In group VI, recipients received no systemic immunosuppression. Assessment included evaluation of transplant viability and induction of donor-specific chimerism via flow cytometry, immunofluorescence, and PCR. Results: Groups III, IV, and VI rejected allografts, at an average of 14+/-5.2, 10+/-2.7, and 8+/-0.7 days. In groups I, II, and V, the mean survival was 80+/-18.2 (p=0.0002), 64+/-27.4 (p=0.001), and 30+/-4.7 (p=0.02) days. In groups I and II, donor-specific chimerism in the blood decreased from 8.8+/-3.4% and 8.6+/-3.4% on day 7 to 3.7+/-1.32% (p=0.02) and 4.7+/-2.7% when the flaps manifested grade 3 rejection. The presence of PKH-26 1 Lewis BMC was confirmed in the donor's blood, bone marrow, lymphoid organs, and liver (preconditioned at 24 and 72 hours). Conclusions: Donor preconditioning is a novel approach modifying recipient's responsiveness to donor allograft and prolonging the allograft survival under short-term immunosuppression. (C) 2016 Wiley Periodicals, Inc.