title: Human Adipose-Derived Mesenchymal Stem Cells Modulate Experimental Autoimmune Arthritis by Modifying Early Adaptive T Cell Responses.
abstract: Mesenchymal stem cells (MSCs) are multipotent stromal cells with immunosuppressive properties. They have emerged as a very promising treatment for autoimmunity and inflammatory diseases such as rheumatoid arthritis. Recent data have identified that GM-CSF-expressing CD4 T cells and Th17 cells have critical roles in the pathogenesis of arthritis and other inflammatory diseases. Although many studies have demonstrated that MSCs can either prevent or suppress inflammation, no studies have addressed their modulation on GM-CSF-expressing CD4 T cells and on the plasticity of Th17 cells. To address this, a single dose of human expanded adipose-derived mesenchymal stem cells (eASCs) was administered to mice with established collagen-induced arthritis. A beneficial effect was observed soon after the infusion of the eASCs as shown by a significant decrease in the severity of arthritis. This was accompanied by reduced number of pathogenic GM-CSF(+) CD4(+) T cells in the spleen and peripheral blood and by an increase in the number of different subsets of regulatory T cells like FOXP3(+) CD4(+) T cells and IL10(+) IL17(-) CD4(+) T cells in the draining lymph nodes (LNs). Interestingly, increased numbers of Th17 cells coexpressing IL10 were also found in draining LNs. These results demonstrate that eASCs ameliorated arthritis after the onset of the disease by reducing the total number of pathogenic GM-CSF(+) CD4(+) T and by increasing the number of different subsets of regulatory T cells in draining LNs, including Th17 cells expressing IL10. All these cellular responses, ultimately, lead to the reestablishment of the regulatory/inflammatory balance in the draining LNs.
authors.affiliation: Unidad Mixta de Terapias Avanzadas, CIEMAT/IIS Fundación Jiménez Díaz/CIBERER, Madrid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Lopez-Santalla
authors.affiliation: TiGenix SAU, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Mancheño-Corvo
authors.affiliation: TiGenix SAU, Madrid, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Menta
authors.affiliation: FARMACROS, Albacete, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Lopez-Belmonte
authors.affiliation: TiGenix SAU, Madrid, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: DelaRosa
authors.affiliation: Unidad Mixta de Terapias Avanzadas, CIEMAT/IIS Fundación Jiménez Díaz/CIBERER, Madrid, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Bueren
authors.affiliation: TiGenix NV, Leuven, Belgium.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Dalemans
authors.affiliation: TiGenix SAU, Madrid, Spain.
authors.forename: Eleuterio
authors.initials: E
authors.lastname: Lombardo
authors.affiliation: Unidad Mixta de Terapias Avanzadas, CIEMAT/IIS Fundación Jiménez Díaz/CIBERER, Madrid, Spain.
authors.forename: Marina I
authors.initials: MI
authors.lastname: Garin
mesh_terms: D000273:Adipose Tissue / Q000276:immunology*; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000628:therapy*; D005260:Female; D064593:Heterografts; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D008811:Mice, Inbred DBA; D058504:Th17 Cells / Q000276:immunology*
keywords: Adipose-derived mesenchymal stem cells; Arthritis; GM-CSF-expressing CD4 T cells; Plasticity of Th17 cells; Regulatory T cells