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Human Fibroblasts Share Immunosuppressive Properties with Bone Marrow Mesenchymal Stem Cells

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Abstract

Introduction

Bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue-derived stem cells share immunosuppressive capacities, suggesting that the latter could be a general property of stromal cells.

Methods

To check this hypothesis, we compared human BM-MSC and fibroblasts for their in vitro multi-potentiality, expandability and their immunomodulatory properties under normalized optimized culture conditions.

Results

We report that, unlike BM-MSCs, fibroblasts cannot differentiate in vitro into adipocytes and osteoblasts and differ from BM-MSCs by the expression of membrane CD106, CD10 and CD26 and by the expression of collagen VII mRNA. Like BM-MSCs, fibroblasts are unable to provoke in vitro allogeneic reactions, but strongly suppress lymphocyte proliferation induced by allogeneic mixed lymphocyte culture (MLC) or mitogens. We show that fibroblasts' immunosuppressive capacity is independent from prostaglandin E2, IL-10 and the tryptophan catabolising enzyme indoleamine 2,3-dioxygenase and is not abrogated after the depletion of CD8+ T lymphocytes, NK cells and monocytes.

Conclusion

Finally, fibroblasts and BM-MSCs act at an early stage through blockage of lymphocyte activation, as demonstrated by down-regulation of GZMB (granzyme B) and IL2RA (CD25) expression.

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Acknowledgments

This study was supported by the Ministère Français de la Recherche (EA3034) and Région Midi-Pyrénées. We thank Christine Bousquet, Christine Taureau and Mélanie Gadelorge for excellent technical assistance. We also thank Sabrina Kellouche (INSERM U553, Paris, France) for providing us with adult dermal fibroblasts.

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Authors and Affiliations

  1. Etablissement Français du sang Pyrénées—Méditerranée, Toulouse, France

    Sandrine Cappellesso-Fleury & Philippe Bourin

  2. Groupement d’Etude des Cellules Souches Mésenchymateuses (GECSOM), Toulouse, France

    Sandrine Cappellesso-Fleury & Philippe Bourin

  3. Laboratoire d’Immunogénétique moléculaire, Université Paul Sabatier, Toulouse 3, France

    Bénédicte Puissant-Lubrano, Pol-André Apoil & Antoine Blancher

  4. Laboratoire d’Immunologie, CHU de Toulouse, Toulouse, France

    Bénédicte Puissant-Lubrano, Pol-André Apoil & Antoine Blancher

  5. INSERM U563, Toulouse, France

    Matthias Titeux

  6. Université Paul Sabatier, 118 Route de Narbonne, 31062, Toulouse cedex 4, France

    Peter Winterton

  7. UMR-CNRS 5018, IFR31, Hôpital Rangueil, Toulouse, France

    Louis Casteilla

  8. Laboratoire d’Immunologie, CHU Rangueil, TSA 50032, 31059, Toulouse cedex 9, France

    Antoine Blancher

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  1. Sandrine Cappellesso-Fleury
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  2. Bénédicte Puissant-Lubrano
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Correspondence to Antoine Blancher.

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Cappellesso-Fleury, S., Puissant-Lubrano, B., Apoil, PA. et al. Human Fibroblasts Share Immunosuppressive Properties with Bone Marrow Mesenchymal Stem Cells. J Clin Immunol 30, 607–619 (2010). https://doi.org/10.1007/s10875-010-9415-4

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  • DOI: https://doi.org/10.1007/s10875-010-9415-4

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