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Disparate Effects of Mesenchymal Stem Cells in Experimental Autoimmune Encephalomyelitis and Cuprizone-Induced Demyelination.
Glenn, Justin D; Smith, Matthew D; Kirby, Leslie A; Baxi, Emily G; Whartenby, Katharine A.
Afiliación
  • Glenn JD; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Smith MD; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Kirby LA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Baxi EG; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Whartenby KA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
PLoS One ; 10(9): e0139008, 2015.
Article en En | MEDLINE | ID: mdl-26407166
Mesenchymal stem cells (MSCs) are pleiotropic cells with potential therapeutic benefits for a wide range of diseases. Because of their immunomodulatory properties they have been utilized to treat autoimmune diseases such as multiple sclerosis (MS), which is characterized by demyelination. The microenvironment surrounding MSCs is thought to affect their differentiation and phenotype, which could in turn affect the efficacy. We thus sought to dissect the potential for differential impact of MSCs on central nervous system (CNS) disease in T cell mediated and non-T cell mediated settings using the MOG35-55 experimental autoimmune encephalomyelitis (EAE) and cuprizone-mediated demyelination models, respectively. As the pathogeneses of MS and EAE are thought to be mediated by IFNγ-producing (TH1) and IL-17A-producing (TH17) effector CD4+ T cells, we investigated the effect of MSCs on the development of these two key pathogenic cell groups. Although MSCs suppressed the activation and effector function of TH17 cells, they did not affect TH1 activation, but enhanced TH1 effector function and ultimately produced no effect on EAE. In the non- T cell mediated cuprizone model of demyelination, MSC administration had a positive effect, with an overall increase in myelin abundance in the brain of MSC-treated mice compared to controls. These results highlight the potential variability of MSCs as a biologic therapeutic tool in the treatment of autoimmune disease and the need for further investigation into the multifaceted functions of MSCs in diverse microenvironments and the mechanisms behind the diversity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Desmielinizantes / Encefalomielitis Autoinmune Experimental / Células Madre Mesenquimatosas Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Desmielinizantes / Encefalomielitis Autoinmune Experimental / Células Madre Mesenquimatosas Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos