title: 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.
abstract: OBJECTIVE
  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 × 106Lewis 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-αβ-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-αβ-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+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. © 2015 Wiley Periodicals, Inc. Microsurgery 36:676-683, 2016.
authors.affiliation: Department of Orthopaedics, University of Illinois at Chicago, College of Medicine, Chicago, IL.
authors.forename: Maria
authors.initials: M
authors.lastname: Siemionow
authors.affiliation: Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rampazzo
authors.affiliation: Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH.
authors.forename: Bahar Bassiri
authors.initials: BB
authors.lastname: Gharb
authors.affiliation: Department of Orthopaedics, University of Illinois at Chicago, College of Medicine, Chicago, IL.|Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH.
authors.forename: Joanna
authors.initials: J
authors.lastname: Cwykiel
authors.affiliation: Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Klimczak
authors.affiliation: Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH.
authors.forename: Maria
authors.initials: M
authors.lastname: Madajka
authors.affiliation: Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH.
authors.forename: Serdar
authors.initials: S
authors.lastname: Nasir
authors.affiliation: Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Bozkurt
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006119:Groin; D051381:Rats; D011917:Rats, Inbred Lew; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D063986:Vascularized Composite Allotransplantation