Human Chorionic Mesenchymal Stromal Cells (hCMSCs) Transplantation Ameliorates Motor Function and Prevents CerebellarAtrophy in Rat Model of Cerebellar Ataxia

Background and Aim: Cerebellar ataxias include a range ofneurodegenerative disorders hallmarked by deterioration of cerebellum.Cell replacement therapy (CRT) offers a potential remedy for the diseasesassociated with the central nervous system (CNS). This study was designedto assess the neuro-restorative/protective effects of human chorionic mesenchymal stromal cells (hCMSCs) implantation on a rat model ofcerebellar ataxia induced by 3-acetylpyridine (3-AP) as a neurotoxin.Methods: To begin, hCMSCs were extracted, cultured and theirmesenchymal abilities proofed. Then, experimental ataxia was inducedin twenty-four male adult rats by single injection of 3-AP, and bilateralhCMSCs transplantation in the cerebellum was performed 7 daysafter 3-AP administration in seven of them. After an assessment oftheir motor coordination by Rotarod test and electromyography(EMG)changes by its device their cerebellum was sampled. Their Purkinjeneuron degeneration was analyzed by Fluoro-Jade staining, then thetranscription status of inflammatory, neurotrophic and apoptotic genesassessed by RT-PCR test. We also analyzed the expression level of VEGFand immunohistochemically changes of calbindin.Results: The findings showed that transplantation of hCMSCs in a 3-APmodel of ataxia ameliorated motor coordination and muscle activity,increased cerebellar volumes of molecular and granular layers plus whitematter, decrease degeneration of Purkinje cells, increase transcriptionof neurotrophic factors and decrease the inflammatory changes andapoptosis. We also observed the increase in expression of VEGF andcalbindin.Conclusion: Taken together, human CMSCs could be considered asa suitable candidate for CRT-based therapies with a specific focus oncerebellar ataxia.

کلیدواژه ها:

Mesenchymal stem cells ، Cerebellar ataxia ، 3-acetylpyridine (3-AP) ، Neurotrophic factors ، Motor coordination ، Neurodegeneration ، Inflammation ، Apoptosis