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Use of donor bone marrow mesenchymal stem cells for treatment of skin allograft rejection in a preclinical rat model

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Abstract

Recent studies indicate that mesenchymal stem cells (MSC) exhibit a degree of immune privilege due to their ability to suppress T cell mediated responses causing tissue rejection; however, the impact of allogeneic MSC in the setting of organ transplantation has been poorly investigated so far. The aim of our study was to evaluate the effect of intravenous donor MSC infusion for clinical tolerance induction in allogeneic skin graft transplantations in rats. MSC were isolated from Wistar rats and administered in Sprague-Dawley rats receiving Wistar skin graft with or without cyclosporine A (CsA). Graft biopsies were performed at day 10 post transplantation in all experimental groups for histological and gene expression studies. Intravenous infusion with donor MSC in CsA-treated transplanted rats resulted in prolongation of skin allograft survival compared to control animals. Unexpectedly, donor MSC infusion in immunocompetent rats resulted in a faster rejection as compared to control group. Cytokine expression analysis at the site of skin graft showed that CsA treatment significantly decreased pro-inflammatory cytokines IFN-γ and IL-2 and reduced TNF-α gene expression; however, the level of TNF-α is high in MSC-treated and not immunosuppressed rats. Results of our study in a rat tissue transplantation model demonstrated a possible immunogenic role for donor (allogeneic) MSC, confirming the need of adequate preclinical experimentation before clinical use.

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Acknowledgments

The authors wish to thank Prof. F. Lolli for his assistance with the statistics.

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Authors and Affiliations

  1. Department of Clinical Medicine and Immunological Sciences, Section of Dermatology, University of Siena, Siena, Italy

    Paolo Sbano, Aldo Cuccia & Michele Fimiani

  2. Hematology Unit, Careggi Hospital, Viale Morgagni 85, 50134, Florence, Italy

    Benedetta Mazzanti, Serena Urbani, Alberto Bosi & Riccardo Saccardi

  3. Department of Medical and Surgical Critical Care and Center of Research, Transfer and High Education, “DENOTHE”, University of Florence, Florence, Italy

    Betti Giusti, Ilaria Lapini, Luciana Rossi, Rosanna Abbate, Giuseppina Marseglia, Genni Nannetti & Francesca Torricelli

  4. Section of Pathological Anatomy and Histology, Department of Human Pathology and Oncology, Policlinico Le Scotte, University of Siena, Siena, Italy

    Clelia Miracco

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  1. Paolo Sbano
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Correspondence to Riccardo Saccardi.

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This work was supported by a grant from a collaborative study with the Ministero della Salute and Regione Toscana (D.Lgs. 502,1992), and funding from Fondazione Marchi.

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Sbano, P., Cuccia, A., Mazzanti, B. et al. Use of donor bone marrow mesenchymal stem cells for treatment of skin allograft rejection in a preclinical rat model. Arch Dermatol Res 300, 115–124 (2008). https://doi.org/10.1007/s00403-007-0827-9

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  • DOI: https://doi.org/10.1007/s00403-007-0827-9

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