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Donor Presensitization With Bone Marrow Transfer Of Recipient Origin Facilitates Skin Allograft Survival
Bahar Bassiri Gharb, MD, Antonio Rampazzo, MD, Marja Madajka, PHD, Serdar Nasir, MD, Mehmet Bozkurt, MD, Alexandra Klimczak, PHD, Maria Z. Siemionow, MD, PHD, DSc.
Cleveland Clinic, Cleveland, OH, USA.
PURPOSE: Donor presensitization with the recipient bone marrow 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) rats were presensitized with Lewis(RT1l) bone marrow (80x 106 cells) prior to transplant of a skin 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 (FACS) for donor (RT1a) chimerism, immunofluorescence and immunohistochemistry for cell phenotyping.
RESULTS: 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% on sacrification day. The presence of PKH+ Lewis bone marrow cells was shown within the transplant and in the donor ACI and recipient’s lymphoid organs.
Donor presensitization with bone marrow cells of recipient origin modifies recipient’s responsiveness and extends vascularized skin allograft survival under short-term protocol of αβ-TCR/CsA therapy.
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