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

Abstract : 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-beta1 (TGF-beta) 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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Contributor : Philippe Saas Connect in order to contact the contributor
Submitted on : Wednesday, May 19, 2010 - 12:45:04 PM
Last modification on : Sunday, June 26, 2022 - 1:18:43 AM

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Aisha Nasef, y. Z. Zhang, Christelle Mazurier, Sandrine Bouchet, M. Bensidhoum, et al.. Selected Stro-1-enriched bone marrow stromal cells display a major suppressive effect on lymphocyte proliferation.. International Journal of Laboratory Hematology, Wiley, 2009, 31 (1), pp.9-19. ⟨10.1111/j.1751-553X.2007.00997.x⟩. ⟨inserm-00484856⟩



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