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Human olfactory epithelium-derived stem cells ameliorate histopathological deficits and improve behavioral functions in a rat model of cerebellar ataxia. J Chem Neuroanat 2022 Mar;120:102071

Date

01/21/2022

Pubmed ID

35051594

DOI

10.1016/j.jchemneu.2022.102071

Scopus ID

2-s2.0-85123126055 (requires institutional sign-in at Scopus site)   3 Citations

Abstract

Cell replacement therapy (CRT) is one of the most effective approaches used to alleviate symptoms of neurodegenerative syndromes such as cerebellar ataxia (CA). Human olfactory epithelium mesenchymal stem cells (OE-MSCs) have been recognized as a promising candidate for CRT, due to their distinctive features including immunomodulatory properties and ease of accessible compared to other types of MSCs. Hence, the main goal of our study was to explore the impacts of OE-MSCs transplantation on behavioral, structural, and histological deficiencies in a rat model of CA. After obtained an informed consent from volunteers, OE-MSCs were obtained from their nasal cavity. Then, OE-MSCs were characterized by the positive expression of CD73, CD90, and CD105 as MSCs as well as nestin and vimentin as primitive neuroectodermal stem cells markers. Then, the animals were randomized into three control, 3-acetylpyridine (3-AP) treated, and 3-AP + cell groups. In both experimental groups, the rats received intraperitoneal injection of 3-AP (75 mg/kg), followed by the implantation of OE-MSCs into the cerebellum of 3-AP + cell group. The impact of engrafted OE-MSCs on motor coordination and performance along with biochemical, immunohistochemical, and stereological changes in the cerebellum of the rat models of CA were investigated. According to our findings, the administration of 3-AP decreased the cerebellar GSH concentration. The injection of 3-AP also altered the morphological characteristics of the cerebellar Golgi cells. On the other hand, OE-MSCs transplantation improved motor coordination in CA. Besides, the implantation of OE-MSCs reduced caspase-3 expression and microglia proliferation in the cerebellum upon 3-AP administration. Finally, the transplant of OE-MSCs protected Purkinje cells against 3-AP toxicity. In sum, the present study revealed considerable advantages of OE-MSCs in managing CA animal model.

Author List

Moghaddam MH, Hatari S, Shahidi AMEJ, Nikpour F, Omran HS, Fathi M, Vakili K, Abdollahifar MA, Tizro M, Eskandari N, Raoofi A, Ebrahimi V, Aliaghaei A

Author

Hossein Salehi Omran MD Postdoctoral Researcher in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cerebellar Ataxia
Humans
Mesenchymal Stem Cell Transplantation
Olfactory Mucosa
Rats