Abstract
IntroductionThe goal of this study is to analyze the potential immunosuppressive properties of mesenchymal stem cells (MSC) on T cell proliferation and in collagen-induced arthritis (CIA). An additional aim is to investigate the role of interferon-γ (IFN-γ) in these processes.MethodsMSC were isolated from bone marrow of DBA/1 wild type and IFN-γ receptor knock-out (IFN-γR KO) mice and expanded in vitro. Proliferation of anti-CD3-stimulated CD4+ T cells in the presence or absence of MSC was evaluated by thymidine incorporation. CIA was induced in DBA/1 mice and animals were treated with MSC by intravenous or intraperitoneal injections of wild type or IFN-γR KO MSC.ResultsPurity of enriched MSC cultures was evaluated by flow cytometry and their ability to differentiate into osteoblasts and adipocytes. In vitro, wild type MSC dose-dependently suppressed anti-CD3-induced T cell proliferation whereas IFN-γR KO MSC had a significantly lower inhibitory potential. A role for inducible nitric oxide (iNOS), programmed death ligand-1 (PD-L1) and prostaglandin E2 (PGE2), but not indoleamine 2,3-dioxigenase (IDO), in the T cell inhibition was demonstrated. In vivo, neither wild type nor IFN-γR KO MSC were able to reduce the severity of CIA or the humoral or cellular immune response toward collagen type II.ConclusionsWhereas MSC inhibit anti-CD3-induced proliferation of T cells in vitro, an effect partially mediated by IFN-γ, MSC do not influence in vivo T cell proliferation nor the disease course of CIA. Thus there is a clear discrepancy between the in vitro and in vivo effects of MSC on T cell proliferation and CIA.
Highlights
The goal of this study is to analyze the potential immunosuppressive properties of mesenchymal stem cells (MSC) on T cell proliferation and in collagen-induced arthritis (CIA)
To strengthen the experimental background for future therapy with MSCs, we addressed the effect of MSCs on in vitro and in vivo Tcell proliferation and on CIA in this study
Generation of mesenchymal stem cells and phenotypical analysis MSCs were generated from bone marrow cells of DBA/1 wild-type and DBA/1 IFN-gR interferongamma receptor knockout (KO) mice
Summary
The goal of this study is to analyze the potential immunosuppressive properties of mesenchymal stem cells (MSC) on T cell proliferation and in collagen-induced arthritis (CIA). Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent progenitor cells that can differentiate into cells of the mesenchymal lineage like bone, fat, and cartilage [1]. Due to these characteristics, they have been postulated as attractive candidates for cell-based tissue repair (for instance, to restore cartilage defects) [2,3]. Treatment of collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis, with MSCs has been investigated. We investigated the role of IFN-g by using MSCs isolated from IFN-g receptor knockout (IFN-gR KO) mice
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