Disparate effects of mesenchymal stem cells in experimental autoimmune encephalomyelitis and cuprizone-induced demyelination

Justin D. Glenn, Matthew D. Smith, Leslie A. Kirby, Emily Grace Baxi, Katharine Whartenby

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere0139008
JournalPLoS One
Volume10
Issue number9
DOIs
StatePublished - Sep 25 2015

Fingerprint

Cuprizone
Autoimmune Experimental Encephalomyelitis
Demyelinating Diseases
encephalitis
Stem cells
Mesenchymal Stromal Cells
stem cells
T-cells
autoimmune diseases
sclerosis
Autoimmune Diseases
Multiple Sclerosis
cells
T-lymphocytes
Chemical activation
Cells
T-Lymphocytes
Th17 Cells
central nervous system diseases
therapeutics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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 Grace; Whartenby, Katharine.

In: PLoS One, Vol. 10, No. 9, e0139008, 25.09.2015.

Research output: Contribution to journalArticle

@article{6f144fe496584d87950893044917115b,
title = "Disparate effects of mesenchymal stem cells in experimental autoimmune encephalomyelitis and cuprizone-induced demyelination",
abstract = "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.",
author = "Glenn, {Justin D.} and Smith, {Matthew D.} and Kirby, {Leslie A.} and Baxi, {Emily Grace} and Katharine Whartenby",
year = "2015",
month = "9",
day = "25",
doi = "10.1371/journal.pone.0139008",
language = "English (US)",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - Disparate effects of mesenchymal stem cells in experimental autoimmune encephalomyelitis and cuprizone-induced demyelination

AU - Glenn, Justin D.

AU - Smith, Matthew D.

AU - Kirby, Leslie A.

AU - Baxi, Emily Grace

AU - Whartenby, Katharine

PY - 2015/9/25

Y1 - 2015/9/25

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84947291965&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947291965&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0139008

DO - 10.1371/journal.pone.0139008

M3 - Article

C2 - 26407166

AN - SCOPUS:84947291965

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e0139008

ER -