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Donor presensitization with bone marrow transplant of recipient origin facilitates vascularized skin allograft survival
Bahar Bassiri Gharb MD, Antonio Rampazzo MD, Maria Madajka PHD, Serdar Nasir MD, Mehmet Bozkurt MD, Alexandra Klimczak MD, Maria Siemionow MD PHD DSc
Cleveland Clinic
2010-04-01
Presenter: Bahar Bassiri Gharb
Affidavit:
Director Name:
Author Category: Resident/Fellow
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Introduction: Donor presensitization with bone marrow transplant of recipient origin to create a mixed chimerism is a new approach to induce immunotolerance in composite tissue allotransplantation.
Methods: Fifty allotransplantations between presensitized ACI donors and Lewis recipients were performed in 6 experimental groups. The ACI(RT1a) donors were presensitized with recipients'(Lewis(RT1l)) bone marrow (80x 106 cells) prior to transplant of a vascularized skin (groin) allo-flap. The recipient Lewis bone marrow was stained with PKH26 to evaluate patterns of cell migration. In control groups I, II, III, Lewis recipients received ACI transplant from non--presensitized, 24 and 72 h presensitized donors respectively, without immunosuppression. In groups IV, V and VI recipients of non presensitized, 24h and 72h presensitized flaps were treated with the 7 day protocol of CSA/TCR therapy. Assessment included transplant viability, flow cytometry analysis for donor(RT1a) chimerism, immunofluorescence and immunohistochemistry for cell migration and phenotyping.
Result: Groups I, II and III rejected grafts respectively in average 7, 14 and 9 days post- transplant. Under immunosuppressive therapy, the mean survival of flaps was respectively 59, 80 and 66 days in groups IV, V and VI. Donor specific chimerism(RT1a) in groups V and VI decreased from 8.8% and 11.4% on day 7 to 3.7% and 4.8% at long-term follow-up . The presence of PKH+ Lewis bone marrow cells was confirmed within the ACI origin transplant and in the recipient's lymphoid organs.
Conclusions: Donor presensitization with bone marrow cells of recipient origin modifies recipient's responsiveness and extends vascularized skin allograft survival under short-term protocol of áâTCR/CsA therapy.
