Intravenous Administration of Bone Marrow-Derived Mesenchymal Stem Cells Induces a Switch from Classical to Atypical Symptoms in Experimental Autoimmune Encephalomyelitis

Potent immunosuppressive and regenerative properties of mesenchymal stem cells (MSCs) position them as a novel therapy for autoimmune diseases. This research examines the therapeutic effect of MSCs administration at different disease stages in experimental autoimmune encephalomyelitis (EAE). Classic...

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Main Authors: Mónica Kurte, Javiera Bravo-Alegría, Alexander Torres, Vania Carrasco, Cristina Ibáñez, Ana María Vega-Letter, Catalina Fernández-O’Ryan, Carlos E. Irarrázabal, Fernando E. Figueroa, Rodrigo A. Fuentealba, Claudia Riedel, Flavio Carrión
Format: Article
Language:English
Published: Hindawi Limited 2015-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2015/140170
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spelling doaj-fe5da1fb37a24073bcfaaec3d0839bad2020-11-24T22:53:47ZengHindawi LimitedStem Cells International1687-966X1687-96782015-01-01201510.1155/2015/140170140170Intravenous Administration of Bone Marrow-Derived Mesenchymal Stem Cells Induces a Switch from Classical to Atypical Symptoms in Experimental Autoimmune EncephalomyelitisMónica Kurte0Javiera Bravo-Alegría1Alexander Torres2Vania Carrasco3Cristina Ibáñez4Ana María Vega-Letter5Catalina Fernández-O’Ryan6Carlos E. Irarrázabal7Fernando E. Figueroa8Rodrigo A. Fuentealba9Claudia Riedel10Flavio Carrión11Laboratory of Cellular and Molecular Immunology, Faculty of Medicine, University of Los Andes, 750000 Santiago, ChileLaboratory of Cellular and Molecular Immunology, Faculty of Medicine, University of Los Andes, 750000 Santiago, ChileLaboratory of Cellular and Molecular Immunology, Faculty of Medicine, University of Los Andes, 750000 Santiago, ChileLaboratory of Cellular and Molecular Immunology, Faculty of Medicine, University of Los Andes, 750000 Santiago, ChileLaboratory of Cellular and Molecular Immunology, Faculty of Medicine, University of Los Andes, 750000 Santiago, ChileLaboratory of Cellular and Molecular Immunology, Faculty of Medicine, University of Los Andes, 750000 Santiago, ChileLaboratory of Cellular and Molecular Immunology, Faculty of Medicine, University of Los Andes, 750000 Santiago, ChileLaboratory of Integrative and Molecular Physiology, Faculty of Medicine, University of Los Andes, 750000 Santiago, ChileLaboratory of Cellular and Molecular Immunology, Faculty of Medicine, University of Los Andes, 750000 Santiago, ChileLaboratory of Cellular and Molecular Immunology, Faculty of Medicine, University of Los Andes, 750000 Santiago, ChileDepartment of Biological Sciences, Faculty of Biological Sciences, Andrés Bello National University, 8370146 Santiago, ChileLaboratory of Cellular and Molecular Immunology, Faculty of Medicine, University of Los Andes, 750000 Santiago, ChilePotent immunosuppressive and regenerative properties of mesenchymal stem cells (MSCs) position them as a novel therapy for autoimmune diseases. This research examines the therapeutic effect of MSCs administration at different disease stages in experimental autoimmune encephalomyelitis (EAE). Classical and atypical scores of EAE, associated with Th1 and Th17 response, respectively, and also Treg lymphocytes, were evaluated. MSCs administration at the onset (EAE+MSConset) induced an important amelioration of the clinical signs and less lasting effect at the peak of EAE (EAE+MSCpeak). No effect was observed when MSCs were applied after EAE stabilization (EAE+MSClate). Surprisingly, EAE atypical signs were detected in EAE+MSCpeak and EAE+MSClate mice. However, no correlation was found in Th17/Th1 ratio. Interestingly, regardless of time administration, MSCs significantly reduced IL-6 and also T-bet, RORγT, and Foxp3 mRNA levels in brain samples of EAE mice. The downregulation of IL-6 could restore the well-functioning of the blood-brain barrier of EAE mice, correlated with a decreased number of brain infiltrating leukocytes. These results suggest that the inflammatory status is important to be considered for administering MSCs in autoimmune pathologies, leading to a further research to clarify the effect of MSCs for multiple sclerosis.http://dx.doi.org/10.1155/2015/140170
collection DOAJ
language English
format Article
sources DOAJ
author Mónica Kurte
Javiera Bravo-Alegría
Alexander Torres
Vania Carrasco
Cristina Ibáñez
Ana María Vega-Letter
Catalina Fernández-O’Ryan
Carlos E. Irarrázabal
Fernando E. Figueroa
Rodrigo A. Fuentealba
Claudia Riedel
Flavio Carrión
spellingShingle Mónica Kurte
Javiera Bravo-Alegría
Alexander Torres
Vania Carrasco
Cristina Ibáñez
Ana María Vega-Letter
Catalina Fernández-O’Ryan
Carlos E. Irarrázabal
Fernando E. Figueroa
Rodrigo A. Fuentealba
Claudia Riedel
Flavio Carrión
Intravenous Administration of Bone Marrow-Derived Mesenchymal Stem Cells Induces a Switch from Classical to Atypical Symptoms in Experimental Autoimmune Encephalomyelitis
Stem Cells International
author_facet Mónica Kurte
Javiera Bravo-Alegría
Alexander Torres
Vania Carrasco
Cristina Ibáñez
Ana María Vega-Letter
Catalina Fernández-O’Ryan
Carlos E. Irarrázabal
Fernando E. Figueroa
Rodrigo A. Fuentealba
Claudia Riedel
Flavio Carrión
author_sort Mónica Kurte
title Intravenous Administration of Bone Marrow-Derived Mesenchymal Stem Cells Induces a Switch from Classical to Atypical Symptoms in Experimental Autoimmune Encephalomyelitis
title_short Intravenous Administration of Bone Marrow-Derived Mesenchymal Stem Cells Induces a Switch from Classical to Atypical Symptoms in Experimental Autoimmune Encephalomyelitis
title_full Intravenous Administration of Bone Marrow-Derived Mesenchymal Stem Cells Induces a Switch from Classical to Atypical Symptoms in Experimental Autoimmune Encephalomyelitis
title_fullStr Intravenous Administration of Bone Marrow-Derived Mesenchymal Stem Cells Induces a Switch from Classical to Atypical Symptoms in Experimental Autoimmune Encephalomyelitis
title_full_unstemmed Intravenous Administration of Bone Marrow-Derived Mesenchymal Stem Cells Induces a Switch from Classical to Atypical Symptoms in Experimental Autoimmune Encephalomyelitis
title_sort intravenous administration of bone marrow-derived mesenchymal stem cells induces a switch from classical to atypical symptoms in experimental autoimmune encephalomyelitis
publisher Hindawi Limited
series Stem Cells International
issn 1687-966X
1687-9678
publishDate 2015-01-01
description Potent immunosuppressive and regenerative properties of mesenchymal stem cells (MSCs) position them as a novel therapy for autoimmune diseases. This research examines the therapeutic effect of MSCs administration at different disease stages in experimental autoimmune encephalomyelitis (EAE). Classical and atypical scores of EAE, associated with Th1 and Th17 response, respectively, and also Treg lymphocytes, were evaluated. MSCs administration at the onset (EAE+MSConset) induced an important amelioration of the clinical signs and less lasting effect at the peak of EAE (EAE+MSCpeak). No effect was observed when MSCs were applied after EAE stabilization (EAE+MSClate). Surprisingly, EAE atypical signs were detected in EAE+MSCpeak and EAE+MSClate mice. However, no correlation was found in Th17/Th1 ratio. Interestingly, regardless of time administration, MSCs significantly reduced IL-6 and also T-bet, RORγT, and Foxp3 mRNA levels in brain samples of EAE mice. The downregulation of IL-6 could restore the well-functioning of the blood-brain barrier of EAE mice, correlated with a decreased number of brain infiltrating leukocytes. These results suggest that the inflammatory status is important to be considered for administering MSCs in autoimmune pathologies, leading to a further research to clarify the effect of MSCs for multiple sclerosis.
url http://dx.doi.org/10.1155/2015/140170
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