title: Adipose-derived mesenchymal stromal cells modulate experimental autoimmune arthritis by inducing an early regulatory innate cell signature.
abstract: Modulation of innate immune responses in rheumatoid arthritis and other immune-mediated disorders is of critical importance in the clinic since a growing body of information has shown the key contribution of dysregulated innate responses in the progression of the disease. Mesenchymal stromal cells (MSCs) are the focus of intensive efforts worldwide due to their key role in tissue regeneration and modulation of inflammation. In this study, we define innate immune responses occurring during the early course of treatment with a single dose of expanded adipose-derived MSCs (eASCs) in established collagen-induced arthritis. eASCs delay the progression of the disease during the early phase of the disease. This is accompanied by a transient induction of Ly6C+monocytes that differentiate into IL10+F4/80+cells in arthritic mice. Strikingly, the induced IL10+F4/80+myeloid cells preferentially accumulated in the draining lymph nodes. This effect was accompanied with a concomitant declining of their frequencies in the spleens. Our results show that eASCs attenuate the arthritic process by inducing an early innate cell signature that involves a transient induction of Ly6C+monocytes in periphery that differentiate into IL10+F4/80+macrophages. Our findings demonstrate that early regulatory innate cell responses, involving the monocyte compartment, are targeted by the eASCs during the onset of collagen-induced inflammation.
authors.affiliation: Hematopoietic Innovative Therapies DivisionCentro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER)MadridSpain; Advanced Therapy UnitCentro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM)MadridSpain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Lopez-Santalla
authors.affiliation: TiGenix SAU Madrid Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Menta
authors.affiliation: TiGenix SAU Madrid Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Mancheño-Corvo
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: Hematopoietic Innovative Therapies DivisionCentro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER)MadridSpain; Advanced Therapy UnitCentro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM)MadridSpain.
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: Hematopoietic Innovative Therapies DivisionCentro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER)MadridSpain; Advanced Therapy UnitCentro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM)MadridSpain.
authors.forename: Marina I
authors.initials: MI
authors.lastname: Garin
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D050154:Adiposity; D000818:Animals; D001169:Arthritis, Experimental; D001327:Autoimmune Diseases; D002454:Cell Differentiation; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D051379:Mice; D009000:Monocytes; D017154:Stromal Cells; D050378:T-Lymphocytes, Regulatory
keywords: Adipose‐derived mesenchymal stem cells; IL10+F4/80+ macrophages; Ly6C+ monocytes; arthritis