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The Neuroprotective Effect of Conditioned Medium from Human Adipose-Derived Mesenchymal Stem Cells is Impaired by N-acetyl Cysteine Supplementation

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Abstract

Oxidative stress is a common feature in neurodegenerative diseases associated with neuroinflammation, and therefore, has been proposed as a key target for novel therapies for these diseases. Recently, adipose-derived stem cell (ASC)-based cell therapy has emerged as a novel strategy for neuroprotection. In this study, we evaluate the therapeutic role of ASC-conditioned medium (ASC-CM) against H2O2-induced neurotoxicity in a new in vitro model of ec23/brain-derived neurotrophic factor (BDNF)-differentiated human SH-SY5Y neuron-like cells (SH-SY5Yd). In the presence of ASC-CM, stressed SH-SY5Yd cells recover normal axonal morphology (with an almost complete absence of H2O2-induced axonal beading), electrophysiological features, and cell viability. This beneficial effect of ASC-CM was associated with its antioxidant capacity and the presence of growth factors, namely, BDNF, glial cell line-derived neurotrophic factor, and transforming growth factor β1. Moreover, the neuroprotective effect of ASC-CM was very similar to that obtained from treatment with BDNF, an essential factor for SH-SY5Yd cell survival. Importantly, we also found that the addition of the antioxidant agent N-acetyl cysteine to ASC-CM abolished its restorative effect; this was associated with a strong reduction in reactive oxygen species (ROS), in contrast to the moderate decrease in ROS produced by ASC-CM alone. These results suggest that neuronal restorative effect of ASC-CM is associated with not only the release of essential neurotrophic factors, but also the maintenance of an appropriate redox state to preserve neuronal function.

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Acknowledgments

This work has been partially supported by grants from the University of the Basque Country (reference GIU/16), the Basque Government (reference IT747-13), and the Jesus Gangoiti Barrera Foundation. We would like to acknowledge General Research Services from the University of the Basque Country (SGIker, UPV/EHU) for their technical support.

Author Contribution Summary

Teodoro Palomares and María Cordero contributed equally to this paper.

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Authors and Affiliations

  1. Department of Surgery and Radiology and Physical Medicine, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain

    Teodoro Palomares

  2. Departments of Cell Biology and Histology, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain

    María Cordero & Ana Alonso-Varona

  3. Department of Pharmacology, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain

    Cristina Bruzos-Cidon, María Torrecilla & Luisa Ugedo

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  1. Teodoro Palomares
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  2. María Cordero
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  3. Cristina Bruzos-Cidon
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Correspondence to Teodoro Palomares.

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Palomares, T., Cordero, M., Bruzos-Cidon, C. et al. The Neuroprotective Effect of Conditioned Medium from Human Adipose-Derived Mesenchymal Stem Cells is Impaired by N-acetyl Cysteine Supplementation. Mol Neurobiol 55, 13–25 (2018). https://doi.org/10.1007/s12035-017-0714-0

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