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Stem Cells International
Volume 2017 (2017), Article ID 2389753, 15 pages
https://doi.org/10.1155/2017/2389753
Research Article

Allogeneic Adipose-Derived Mesenchymal Stromal Cells Ameliorate Experimental Autoimmune Encephalomyelitis by Regulating Self-Reactive T Cell Responses and Dendritic Cell Function

1Institute of Parasitology and Biomedicine “López-Neyra”, CSIC, PTS, Granada, Spain
2GENYO, Centre of Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS, Granada, Spain
3School of Medicine, Department of Pathology, IBIMER, CIBM, University of Granada, Granada, Spain

Correspondence should be addressed to Per Anderson; se.oyneg@nosredna.rep and Mario Delgado; se.cisc.bpi@odagledm

Received 17 October 2016; Accepted 18 December 2016; Published 30 January 2017

Academic Editor: Marcella Franquesa

Copyright © 2017 Per Anderson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Multipotent mesenchymal stromal cells (MSCs) have emerged as a promising therapy for autoimmune diseases, including multiple sclerosis (MS). Administration of MSCs to MS patients has proven safe with signs of immunomodulation but their therapeutic efficacy remains low. The aim of the current study has been to further characterize the immunomodulatory mechanisms of adipose tissue-derived MSCs (ASCs) in vitro and in vivo using the EAE model of chronic brain inflammation in mice. We found that murine ASCs (mASCs) suppress T cell proliferation in vitro via inducible nitric oxide synthase (iNOS) and cyclooxygenase- (COX-) 1/2 activities. mASCs also prevented the lipopolysaccharide- (LPS-) induced maturation of dendritic cells (DCs) in vitro. The addition of the COX-1/2 inhibitor indomethacin, but not the iNOS inhibitor L-NAME, reversed the block in DC maturation implicating prostaglandin (PG) E2 in this process. In vivo, early administration of murine and human ASCs (hASCs) ameliorated myelin oligodendrocyte protein- (MOG35-55-) induced EAE in C57Bl/6 mice. Mechanistic studies showed that mASCs suppressed the function of autoantigen-specific T cells and also decreased the frequency of activated (CD11c+ and CD11c+TNF-α+) DCs in draining lymph nodes (DLNs). In summary, these data suggest that mASCs reduce EAE severity, in part, through the impairment of DC and T cell function.