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Neuroprotective mesenchymal stem cells are endowed with a potent antioxidant effect in vivo
Author(s) -
Lanza Cristina,
Morando Sara,
Voci Adriana,
Canesi Laura,
Principato Maria Cristina,
Serpero Laura Domenica,
Mancardi Gianluigi,
Uccelli Antonio,
Vergani Laura
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06268.x
Subject(s) - neuroprotection , experimental autoimmune encephalomyelitis , oxidative stress , superoxide dismutase , neurodegeneration , inflammation , mesenchymal stem cell , antioxidant , in vivo , glutathione peroxidase , biology , chemistry , immunology , pharmacology , biochemistry , microbiology and biotechnology , medicine , disease
Experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis, is characterized by demyelination, inflammation and neurodegeneration of CNS in which free radicals play a role. Recently, the efficacy of murine mesenchimal stem cells (MSCs) as treatment of EAE induced in mice by the encephalitogenic peptide MOG(35–55) was demonstrated. The present study analyzed some markers of oxidative stress, inflammation/degeneration and apoptosis such as metallothioneins (MTs), antioxidant enzymes (superoxide dismutase, catalase and glutathione‐ S ‐transferase), poly(ADP‐ribose) polymerase‐1 and p53 during EAE progression and following MSC treatment. Expression of the three brain MT isoforms increased significantly in EAE mice compared with healthy controls, but while expression of MT‐1 and MT‐3 increased along EAE course, MT‐2 was up‐regulated at the onset, but returned to levels similar to those of controls in chronic phase. The changes in the transcription and activity of the antioxidant enzymes and in expression of poly(ADP‐ribose) polymerase‐1 and p53 showed the same kinetics observed for MT‐1 and MT‐3 during EAE. Interestingly, i.v. administration of MSCs reduced the EAE‐induced increases in levels/activities of all these proteins. These results support an antioxidant and neuroprotective activity for MSCs that was also confirmed in vitro on neuroblastoma cells exposed to an oxidative insult.