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High Throughput Characterization of Adult Stem Cells Engineered for Delivery of Therapeutic Factors for Neuroprotective Strategies
Published on: January 4, 2015
Neuroprotective mesenchymal stem cells are endowed with a potent antioxidant effect in vivo
Cristina Lanza1, Sara Morando, Adriana Voci
1Department of Biology, University of Genoa, Genoa 16132, Italy.
Abstract:
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.
Insights
Mesenchymal stem cells (MSCs) show promise in treating experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. MSCs reduced oxidative stress and neurodegeneration markers, suggesting antioxidant and neuroprotective effects.
Area of Science:
- Neuroscience
- Immunology
- Stem Cell Biology
Background:
- Experimental autoimmune encephalomyelitis (EAE) is a model for multiple sclerosis, involving CNS demyelination, inflammation, and neurodegeneration.
- Free radicals and oxidative stress are implicated in EAE pathogenesis.
- Murine mesenchymal stem cells (MSCs) have shown efficacy in treating EAE.
Purpose of the Study:
- To analyze oxidative stress, inflammation/degeneration, and apoptosis markers during EAE progression.
- To investigate the effects of MSC treatment on these markers in EAE.
- To confirm MSCs' antioxidant and neuroprotective potential in vitro.
Main Methods:
- Induction of EAE in mice using the MOG(35-55) peptide.
- Analysis of metallothioneins (MTs), antioxidant enzymes (superoxide dismutase, catalase, glutathione-S-transferase), PARP-1, and p53 expression and activity.
- Intravenous administration of MSCs to EAE mice.
- In vitro experiments on neuroblastoma cells exposed to oxidative stress.
Main Results:
- EAE mice exhibited increased expression of MT isoforms (MT-1, MT-2, MT-3), antioxidant enzymes, PARP-1, and p53 compared to controls.
- MSC treatment significantly reduced the EAE-induced increases in these markers.
- MSCs demonstrated antioxidant and neuroprotective effects in vitro.
Conclusions:
- MSCs possess antioxidant and neuroprotective properties beneficial in EAE.
- MSC therapy may mitigate oxidative stress and neurodegeneration in EAE.
- Further research into MSCs for multiple sclerosis treatment is warranted.
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