Ezio Gerdoni1, Barbara Gallo2, Simona Casazza1, Silvia Musio2, Ivan Bonanni1, Enrico Pedemonte1, Renato Mantegazza2, Francesco Frassoni3, Gianluigi Mancardi4,1, Rosetta Pedotti2, Antonio Uccelli4,1
1Neuroimmunology Unit, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Italy
2Immunology and Muscular Pathology Unit, National Neurological Institute “C. Besta,” Milan, Italy
3Department of Haematology, San Martino Hospital, Italy
4Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy
Tóm tắt
AbstractObjectiveTo evaluate the ability of mesenchymal stem cells (MSCs), a subset of adult stem cells from bone marrow, to cure experimental autoimmune encephalomyelitis.MethodsThe outcome of the injection of MSCs, in mice immunized with the peptide 139–151 of the proteolipid protein (PLP), was studied analyzing clinical and histological scores of treated mice. The fate of MSCs labeled with the green fluorescent protein was tracked in vivo by a photon emission imaging system and postmortem by immunofluorescence. The modulation of the immune response against PLP was studied through the analysis of in vivo T‐ and B‐cell responses and by the adoptive transfer of MSC‐treated encephalitogenic cells.ResultsMSC‐treated mice showed a significantly milder disease and fewer relapses compared with control mice, with decreased number of inflammatory infiltrates, reduced demyelination, and axonal loss. In contrast, no evidence of green fluorescent protein–labeled neural cells was detected inside the brain parenchyma, thus not supporting the hypothesis of MSCs transdifferentiation. In vivo, PLP‐specific T‐cell response and antibody titers were significantly lower in MSC‐treated mice. When adoptively transferred, encephalitogenic T cells activated against PLP139–151 in the presence of MSCs induced a milder disease compared with that induced by untreated encephalitogenic T cells. These cells showed decreased production of interferon‐γ and tumor necrosis factor‐α and did not proliferate on antigen recall, and thus were considered anergic.InterpretationOverall, these findings suggest that the beneficial effect of MSCs in experimental autoimmune encephalomyelitis is mainly the result of an interference with the pathogenic autoimmune response. Ann Neurol 2007;61:219–227
