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Human Umbilical Cord Matrix Stem Cells Reverse Oxidative Stress-Induced Cell Death and Ameliorate Motor Function and Striatal Atrophy in Rat Model of Huntington Disease

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Abstract

Huntington disease (HD) is an inherited disorder hallmarked by progressive deterioration of specific neurons, followed by movement and cognitive anomalies. Cell therapy approaches in neurodegenerative conditions have concentrated on the replenishment of lost/dying neurons with functional ones. Multipotent mesenchymal stem cells (MSCs) have been represented as a potential remedy for HD. In this study, we evaluated the in vitro and in vivo efficacy of umbilical cord matrix stem cells (UCMSCs) and their paracrine effect against oxidative stress with a specific focus on HD. To this end, UCMSCs were isolated, immunophenotypically characterized by the positive expression of MSC markers, and exhibited multilineage potentiality. Besides, synthesis of neurotrophic factors of GDNF and VEGF by UCMSC was confirmed. Initially, PC12 cells were exposed to superoxide in the presence of conditioned media (CM) collected from UCMSC (UCMSC-CM) and cell viability plus neuritogenesis were measured. Next, bilateral striatal transplantation of UCMSC in 3-nitropropionic acid (3-NP) lesioned rat models was conducted, and 1 month later, post-graft analysis was performed. According to our in vitro results, CM of UCMSC protected PC12 cells against oxidative stress and considerably enhanced cell viability and neurite outgrowth. On the other hand, transplanted UCMSC survived, decreased gliosis, and ameliorated motor coordination and muscle activity, along with an increase in striatal volume as well as in dendritic length of the striatum in HD rats. Collectively, our findings imply that UCMSCs provide an enriched platform by largely their paracrine factors, which downgrades the unfavorable effects of oxidative stress.

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Acknowledgements

The present research work was supported by Vice Chancellor of Neuroscience Reserch Center of Shahid Beheshti University of Medical Sciences and this project is part of M.D. thesis of MJ. Ebrahimi.

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Authors and Affiliations

  1. Cell Biology and Anatomical Sciences, School Of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammad Javad Ebrahimi, Abbas Aliaghaei, Mohammad Amin Abdollahifar, Houssein Ahmadi & Yousef Sadeghi

  2. Department Of Stem Cells and Rgenerative Medicine, Faculty of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

    Mahdi Eskandarian Boroujeni

  3. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Fariba Khodagholi & Mahtab Daftari

  4. Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Gholamhoussein Meftahi

  5. Neurophysiology Research Center, Shahid Beheshti University Of Medical Sciences, Tehran, Iran

    Samira Danyali

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  1. Mohammad Javad Ebrahimi
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Correspondence to Yousef Sadeghi.

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The Ethics Committee of the University approved this animal experiment (IR SBMU.PHNS.REC.1395.7).

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Electronic supplementary material

Supplementary Fig. 1

The site of transplanted cells in the striatum. The implanted cells stained with hematoxylin were injected in the striatum and were still detectable after one month. The dashed line showed the site of injection. Magnification: 10X. (DOCX 281 kb).

ESM 1

The stats for rotarod test performance over the 4-week period. (XLSX 14 kb).

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Ebrahimi, M.J., Aliaghaei, A., Boroujeni, M.E. et al. Human Umbilical Cord Matrix Stem Cells Reverse Oxidative Stress-Induced Cell Death and Ameliorate Motor Function and Striatal Atrophy in Rat Model of Huntington Disease. Neurotox Res 34, 273–284 (2018). https://doi.org/10.1007/s12640-018-9884-4

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  • DOI: https://doi.org/10.1007/s12640-018-9884-4

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