Neuroprotective mesenchymal stem cells are endowed with a potent antioxidant effect in vivo

• Published in: Journal of neurochemistry Vol. 110; no. 5; pp. 1674 - 1684
• Main Authors: Lanza, Cristina, Morando, Sara, Voci, Adriana, Canesi, Laura, Principato, Maria Cristina, Serpero, Laura Domenica, Mancardi, Gianluigi, Uccelli, Antonio, Vergani, Laura
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.09.2009; Blackwell Publishing Ltd; Wiley-Blackwell
• Subjects: Animals; Antioxidants - metabolism; Biochemistry; Biological and medical sciences; Cell Line, Tumor; CNS; Culture Media, Conditioned - metabolism; Encephalomyelitis, Autoimmune, Experimental - metabolism; Encephalomyelitis, Autoimmune, Experimental - prevention & control; experimental autoimmune encephalomyelitis; Female; Free radicals; Humans; Medical sciences; mesenchimal stem cells; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; metallothionein; Metallothionein - metabolism; Mice; Mice, Inbred C57BL; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; oxidative stress; Oxidative Stress - physiology; Rodents; Stem cells; Tumors of the nervous system. Phacomatoses; Autoimmunity; Animal model; Oxidative stress; Multiple sclerosis; Encephalomyelitis; Peptides; Stem cell; Central nervous system; Autoimmune disease; CNS; metallothionein; Free radical; Inflammatory disease; experimental autoimmune encephalomyelitis; Degeneration; Human; Immunopathology; Nervous system diseases; Rodentia; Inflammation; Malignant tumor; Antioxidant; mesenchimal stem cells; Cerebral disorder; Vertebrata; Mammalia; Treatment; Mouse; Central nervous system disease; Autonomic neuropathy; Spinal cord disease; Cancer
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2009.06268.x

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.