Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Anatomical Sciences, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran.
Metab Brain Dis. 2020 Apr;35(4):615-625. doi: 10.1007/s11011-020-00543-0. Epub 2020 Feb 15.
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.
小脑共济失调（CA）是一种影响小脑的共济失调形式。细胞替代疗法（CRT）已被认为是治疗神经紊乱的一种潜在疗法。在本报告中，我们研究了人胚干细胞（HCSCs）移植对 3-乙酰吡啶（3-AP）诱导的 CA 大鼠模型的神经修复作用。在这方面，我们分离并表型鉴定了 HCSCs。接下来，通过单次注射 3-AP 诱导共济失调，在 3-AP 注射后 3 天进行双侧 HCSCs 移植，然后分析许多凋亡、自噬和炎症基因的表达以及血管内皮生长因子（VEGF）水平，并评估小脑神经退行性变、运动协调和肌肉活动。研究结果表明，在 3-AP 诱导的共济失调模型中移植 HCSCs 可降低几种炎症、自噬和凋亡基因的表达水平，并上调小脑区域的 VEGF，防止 3-AP 毒性引起的浦肯野细胞退化，并改善运动协调和肌肉功能。总之，这些数据表明 HCSCs 在重建运动技能和逆转 CA 方面具有体内疗效。
