Local administration of Mitomycin-C-Treated peripheral blood mononuclear cells (PBMCs) prolongs allograft survival in vascularized composite allotransplantation

Christian Andreas Radu, Jurij Kiefer, Martha Maria Gebhard, Amir Khosrow Bigdeli, Volker Jürgen Schmidt, Guenter Germann, Marcus Lehnhardt, Peter Terness, Ulrich Kneser, Thomas Kremer

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    Abstrakt

    BACKGROUND: VCA offers a potential treatment for extensive tissue defects. First results of systemic administration of Mitomycin C-treated PBMCs in VCA demonstrated a significant prolongation of allograft survival. The aim of this study is to evaluate if local administration of MMC-PBMCs prolongs allograft survival in allogeneic hind limb transplantations of the rat.

    METHODS: Sixty allogeneic hind limb transplantations in the rat were performed in six groups. Lewis rats (LEW) were used as hind limb donors and Brown-Norway rats (BN) as recipients. Animals in group A received donor-derived MMC-treated PBMCs locally (i.m.). Group B received no immunosuppressive therapy, group C received a standard immunosuppressive regime consisting of FK506 and Prednisolon, group D (BN to BN) comprised isograft transplantations without immunosuppressive treatment, group E received non-treated PBMCs (i.m.) and group F received phosphate buffered saline (PBS) without cells. The transplanted hind limbs were assessed for color, edema, skin, hair condition, and consistency of the thigh every 8 hours.

    RESULTS: Rejection in group A was delayed to an average of 7.2 ± 0.6 days. Survival times were significantly prolonged (P < 0.01) compared to control groups B, E, and F (5.5 ± 0.7, 5.8 ± 0.7, and 5.7 ± 0.5 days). Control groups C and D showed no signs of rejection.

    CONCLUSION: The findings of this study show that local administration of MMC-PBMCs has no side effects and significantly extends allograft survival. Further experiments with MMC-PBMCs treatments repeated at different time-points and being added to low dose immunosuppressive protocols need to be performed to improve experimental and eventually clinical outcome after VCA. © 2015 Wiley Periodicals, Inc. Microsurgery 36:417-425, 2016.

    OriginalsprogEngelsk
    Sider (fra-til)417-425
    Antal sider9
    TidsskriftMicrosurgery
    Vol/bind36
    Udgave nummer5
    DOI
    StatusUdgivet - jul. 2016

    Bibliografisk note

    © 2015 Wiley Periodicals, Inc.

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