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Olfactory mucosa stem cells delivery via nasal route: a simple way for the treatment of Parkinson disease

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Abstract

Finding a simple and effective way for transferring cells to the brain lesion site with minimum side effects mounts a challenge in cell therapy. Cell delivery via nasal route using the bypassing the blood-brain barrier (BBB) property is a simple and non-invasive strategy without serious complications such as trauma. Therefore, it is a suitable technique to treat neurodegenerative disorders like Parkinson’s disease (PD). Olfactory ectomesenchymal stem cells (OE-MSCs) located in the lamina propria of olfactory mucosa could be differentiated into dopaminergic neurons under in vitro and in vivo conditions. Thus, OE-MSCs represent a good source of Parkinson’s stem cell–based therapy. In this research, we studied thirty male rats (n = 10 in each group) in three control (Ctl), lesion (LE), and intranasal administration (INA) groups to investigate the therapeutic effect of intranasal injection of OE-MSCs in the Parkinson’s animal models. To do so, we examined the homing variation of OE-MSCs in different brain regions such as olfactory bulb (OB), cortex, striatum (Str), hippocampus (HPC), and substantia nigra (SN). The results of real-time PCR and immunohistochemistry (IHC) analysis showed the expression of dopaminergic neuron markers such as PITX3, PAX2, PAX5 (as dopaminergic neurons markers), tyrosine hydroxylase (TH), and dopamine transporter (DAT) 2 months after INA of 1 × 106 OE-MSCs. The results confirmed that IN OE-MSCs delivery into the central nervous system (CNS) was powerful enough to improve the behavioral functions in the animal models of PD.

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Data Availability

We would like to declare that data supporting the study findings can be provided within the paper or supplementary materials.

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Acknowledgments

This work was funded by Iran University of Medical Sciences [grant no. 29348]. The authors would like to thank Dr. Kamran Kamrava and Dr. Maryam Jalessi from ENT and Head and Neck Research Center in Hazrat Rasoul Akram Hospital for their support of this paper.

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Author notes

  1. Sara Simorgh and Rafieh Alizadeh contributed equally to this work.

Authors and Affiliations

  1. Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran

    Sara Simorgh

  2. ENT and Head & Neck Research Center and Department, The Five Senses Institute, HazratRasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran

    Rafieh Alizadeh

  3. Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Ronk Shabani, Elham Seidkhani, Jamal Majidpoor & Fatemeh Moradi

  4. Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran

    Ronk Shabani, Fariba Karimzadeh & Fatemeh Moradi

  5. Department of chemical engineering, Universitat Politècnica de Catalunya, Barcelona, Spain

    Hamidreza Kasbiyan

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  1. Sara Simorgh
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Contributions

Rafieh Alizadeh and Fatemeh Moradi were contributed to the conception and design stages of the study. The isolation and preparation of OE-MSCs were performed by Sara Simorgh and Fariba Karimzadeh. The flow cytometry analysis was conducted by Elham Seidkhani. The first draft of the paper was written by Sara Simorgh and Hamidreza Kasbiyan, and then read and revised by all the authors. Moreover, the final version of the manuscript was confirmed by all the authors prior to the submission.

Corresponding authors

Correspondence to Fatemeh Moradi or Hamidreza Kasbiyan.

Ethics declarations

The study protocols have been approved by the ethical committee of Iran University of Medical Sciences (ethical code: IR.IUMS.REC1395.95-03-30-29348).

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The authors declare that they have no conflict of interest.

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Simorgh, S., Alizadeh, R., Shabani, R. et al. Olfactory mucosa stem cells delivery via nasal route: a simple way for the treatment of Parkinson disease. Neurotox Res 39, 598–608 (2021). https://doi.org/10.1007/s12640-020-00290-1

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  • DOI: https://doi.org/10.1007/s12640-020-00290-1

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