Mesenchymal stem cells effectively modulate pathogenic immune response in experimental autoimmune encephalomyelitis.
OBJECTIVE
To evaluate the ability of mesenchymal stem cells (MSCs), a subset of adult stem cells from bone marrow, to cure experimental autoimmune encephalomyelitis.


METHODS
The 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.


RESULTS
MSC-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 PLP(139-151) 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-gamma and tumor necrosis factor-alpha and did not proliferate on antigen recall, and thus were considered anergic.


CONCLUSIONS
Overall, 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.
Gerdoni
Ezio
E
Neuroimmunology Unit, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Genova, Italy.
Gallo
Barbara
B
Casazza
Simona
S
Musio
Silvia
S
Bonanni
Ivan
I
Pedemonte
Enrico
E
Mantegazza
Renato
R
Frassoni
Francesco
F
Mancardi
Gianluigi
G
Pedotti
Rosetta
R
Uccelli
Antonio
A
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151); D049452:Green Fluorescent Proteins