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Grafted human chorionic stem cells restore motor function and preclude cerebellar neurodegeneration in rat model of cerebellar ataxia

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Abstract

Cerebellar ataxia (CA) is a form of ataxia that adversely affects the cerebellum. Cell replacement therapy (CRT) has been considered as a potential treatment for neurological disorders. In this report, we investigated the neuro-restorative effects of human chorionic stem cells (HCSCs) transplantation on rat model of CA induced by 3-acetylpyridine (3-AP). In this regard, HCSCs were isolated and phenotypically determined. Next, a single injection of 3-AP was administered for ataxia induction, and bilateral HCSCs implantation was conducted 3 days after 3-AP injection, followed by expression analysis of a number of apoptotic, autophagic and inflammatory genes as well as vascular endothelial growth factor (VEGF) level, along with assessment of cerebellar neurodegeneration, motor coordination and muscle activity. The findings revealed that grafting of HCSCs in 3-AP model of ataxia decreased the expression levels of several inflammatory, autophagic and apoptotic genes and provoked the up-regulation of VEGF in the cerebellar region, prevented the degeneration of Purkinje cells caused by 3-AP toxicity and ameliorated motor coordination and muscle function. In conclusion, these data indicate in vivo efficacy of HCSCs in the reestablishment of motor skills and reversal of CA.

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Acknowledgements

The authors would like to thank the Clinical Research Development Unit (CRDU) of Loghman Hakim Hospital and Shahid Beheshti University of Medical Sciences, Tehran, Iran for their support, cooperation and assistance throughout the period of study (grant number 14231).

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Author notes

  1. Mohammadhosein Akhlaghpasand and Mahdi Tizro contributed equally to this work.

Authors and Affiliations

  1. Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammadhosein Akhlaghpasand, Mahdi Tizro & Ali Jahanian

  2. Department of Anatomical Sciences, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Amir Raoofi

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

    Arman Zeinaddini Meymand & Fariba Khodagholi

  4. Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran

    Mohammaderfan Farhadieh

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

    Aysan Khatmi, Reza Soltani & Abbas Aliaghaei

  6. Neurosurgery Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

    Yadolah Hoseini

  7. Department of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland

    Mahdi Eskandarian Boroujeni

Authors
  1. Mohammadhosein Akhlaghpasand
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  2. Mahdi Tizro
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  11. Mahdi Eskandarian Boroujeni
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  12. Abbas Aliaghaei
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Corresponding authors

Correspondence to Mahdi Eskandarian Boroujeni or Abbas Aliaghaei.

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The authors declare that they have no conflict of interest.

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Informed consent was obtained from all individual participants included in the study.

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All experiments were done in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publication No. 80–23, revised 1996) and were approved by the Research and Ethics Committee of Shahid Beheshti University of Medical Sciences, Tehran, Iran, under approval NO. IR. SBMU. REC. 1397.007.

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Akhlaghpasand, M., Tizro, M., Raoofi, A. et al. Grafted human chorionic stem cells restore motor function and preclude cerebellar neurodegeneration in rat model of cerebellar ataxia. Metab Brain Dis 35, 615–625 (2020). https://doi.org/10.1007/s11011-020-00543-0

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