title: Allogeneic Adipose-Derived Mesenchymal Stromal Cells Ameliorate Experimental Autoimmune Encephalomyelitis by Regulating Self-Reactive T Cell Responses and Dendritic Cell Function.
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) E2in 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+CD40highand 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.
authors.affiliation: Institute of Parasitology and Biomedicine "López-Neyra", CSIC, PTS, Granada, Spain; GENYO, Centre of Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS, Granada, Spain.
authors.forename: Per
authors.identifier: 0000-0002-0958-7990
authors.initials: P
authors.lastname: Anderson
authors.affiliation: Institute of Parasitology and Biomedicine "López-Neyra", CSIC, PTS, Granada, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Gonzalez-Rey
authors.affiliation: School of Medicine, Department of Pathology, IBIMER, CIBM, University of Granada, Granada, Spain.
authors.forename: Francisco
authors.identifier: 0000-0001-9207-2287
authors.initials: F
authors.lastname: O'Valle
authors.affiliation: GENYO, Centre of Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS, Granada, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Martin
authors.affiliation: Institute of Parasitology and Biomedicine "López-Neyra", CSIC, PTS, Granada, Spain.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Oliver
authors.affiliation: Institute of Parasitology and Biomedicine "López-Neyra", CSIC, PTS, Granada, Spain.
authors.forename: Mario
authors.identifier: 0000-0003-1893-5982
authors.initials: M
authors.lastname: Delgado