Selected Stro-1-enriched bone marrow stromal cells display a major suppressive effect on lymphocyte proliferation

Authors

  • A. NASEF,

    1. EA 1638 Laboratoire de Thérapie Cellulaire et Radioprotection Accidentelle (LTCRA), Faculté de médecine Saint Antoine, Université Paris VI, Paris, France
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  • Y. Z. ZHANG,

    1. EA 1638 Laboratoire de Thérapie Cellulaire et Radioprotection Accidentelle (LTCRA), Faculté de médecine Saint Antoine, Université Paris VI, Paris, France
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  • C. MAZURIER,

    1. EA 1638 Laboratoire de Thérapie Cellulaire et Radioprotection Accidentelle (LTCRA), Faculté de médecine Saint Antoine, Université Paris VI, Paris, France
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  • S. BOUCHET,

    1. EA 1638 Laboratoire de Thérapie Cellulaire et Radioprotection Accidentelle (LTCRA), Faculté de médecine Saint Antoine, Université Paris VI, Paris, France
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  • M. BENSIDHOUM,

    1. EA 1638 Laboratoire de Thérapie Cellulaire et Radioprotection Accidentelle (LTCRA), Faculté de médecine Saint Antoine, Université Paris VI, Paris, France
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  • S. FRANCOIS,

    1. EA 1638 Laboratoire de Thérapie Cellulaire et Radioprotection Accidentelle (LTCRA), Faculté de médecine Saint Antoine, Université Paris VI, Paris, France
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  • N. C. GORIN,

    1. EA 1638 Laboratoire de Thérapie Cellulaire et Radioprotection Accidentelle (LTCRA), Faculté de médecine Saint Antoine, Université Paris VI, Paris, France
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  • M. LOPEZ,

    1. EA 1638 Laboratoire de Thérapie Cellulaire et Radioprotection Accidentelle (LTCRA), Faculté de médecine Saint Antoine, Université Paris VI, Paris, France
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  • D. THIERRY,

    1. EA 1638 Laboratoire de Thérapie Cellulaire et Radioprotection Accidentelle (LTCRA), Faculté de médecine Saint Antoine, Université Paris VI, Paris, France
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  • L. FOUILLARD,

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    • 1

      These authors contributed equally to this study.

  • A. CHAPEL

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    • 1

      These authors contributed equally to this study.


Loic Fouillard, EA 1638 Laboratoire de Thérapie Cellulaire et Radioprotection Accidentelle (LTCRA), Faculté de médecine Saint Antoine, Université Paris VI, 27 rue de Chaligny, 75012 Paris, France.
Tel.: 33 1 49 28 32 60;
Fax: 33 1 49 28 32 00;
E-mail: loic.fouillard@sat.ap-hop-paris.fr
Alan Chapel E-mail: alain.chapel@irsn.fr Tel: 33 1 58 35 95 46

Summary

Mesenchymal stem cells (MSCs) have an immunosuppressive effect and can inhibit the proliferation of alloreactive T cells in vitro and in vivo. Cotransplantation of MSCs and hematopoietic stem cells (HSCs) from HLA-identical siblings has been shown to reduce the incidence of acute graft-vs.-host disease. MSCs are heterogeneous and data on the inhibitory effects of different MSC subsets are lacking. The antigen Stro1 is a marker for a pure primitive MSC subset. We investigated whether Stro-1-enriched induce a more significant suppressive effect on lymphocytes in a mixed lymphocyte reaction (MLR), and whether this action is related to a specific gene expression profile in Stro-1-enriched compared to other MSCs. We demonstrated that the Stro-1-enriched population elicits a significantly more profound dose-dependent inhibition of lymphocyte proliferation in a MLR than MSCs. One thousand expanded Stro-1-enriched induced an inhibitory effect comparable to that of 10 times as many MSCs. Inhibition by Stro-1-enriched was more significant in contact-dependent cultures than in noncontact-dependant cultures at higher ratio. The Stro-1-enriched inhibitory effect in both culture types was linked to increased gene expression for soluble inhibitory factors such as interleukin-8 (IL-8), leukemia inhibitory factor (LIF), indoleamine oxidase (IDO), human leukocyte antigen-G (HLA-G), and vascular cell adhesion molecule (VCAM1). However, tumor growth factor-β1 (TGF-β) and IL-10 were only up-regulated in contact-dependant cultures. These results may support using a purified Stro-1-enriched population to augment the suppressive effect in allogeneic transplantation.

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