Allogeneic Adipose-Derived Mesenchymal Stromal Cells Ameliorate Experimental Autoimmune Encephalomyelitis by Regulating Self-Reactive T Cell Responses and Dendritic Cell Function
Open Access
- 1 January 2017
- journal article
- research article
- Published by Hindawi Limited in Stem Cells International
- Vol. 2017, 1-15
- https://doi.org/10.1155/2017/2389753
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.
Keywords
Funding Information
- Instituto de Salud Carlos III (PI15/00794, CP09/00228, CPII15/00032, PI12/01097, PI15/02015, RD12/0019/0006, PS09-00928, PSE-010000-2009-3, P09-CTS-4723)
This publication has 69 references indexed in Scilit:
- Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept studyThe Lancet Neurology, 2012
- Mesenchymal stem cells impair in vivo T-cell priming by dendritic cellsProceedings of the National Academy of Sciences of the United States of America, 2011
- The elusive nature and function of mesenchymal stem cellsNature Reviews Molecular Cell Biology, 2011
- Safety and Immunological Effects of Mesenchymal Stem Cell Transplantation in Patients With Multiple Sclerosis and Amyotrophic Lateral SclerosisArchives of Neurology, 2010
- Mesenchymal and haematopoietic stem cells form a unique bone marrow nicheNature, 2010
- The role of dendritic cells in CNS autoimmunityJournal of Molecular Medicine, 2010
- Autoimmune T cell responses in the central nervous systemNature Reviews Immunology, 2009
- Human bone marrow‐derived mesenchymal stem cells induce Th2‐polarized immune response and promote endogenous repair in animal models of multiple sclerosisGlia, 2009
- Multiple sclerosisThe Lancet, 2008
- A Perivascular Origin for Mesenchymal Stem Cells in Multiple Human OrgansCell Stem Cell, 2008