Cell Biology & Anatomical Sciences Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Stem Cells & Regenerative Medicine, Faculty of Medical Biotechnology, National Institute of Genetic Engineering & Biotechnology, Tehran, Iran.
Cell Tissue Res. 2019 May;376(2):179-187. doi: 10.1007/s00441-018-02980-x. Epub 2019 Jan 12.
Cerebellar ataxias (CA) include a range of neurodegenerative disorders hallmarked by deterioration of the cerebellum. Cell replacement therapy (CRT) offers a potential remedy for the diseases associated with the central nervous system (CNS). This study was designed to assess the neurorestorative/protective effects of dental pulp stem cell (DPSC) implantation on a rat model of CA induced by 3-acetylpyridine (3-AP) as a neurotoxin. To begin, human DPSCs were extracted, cultured and phenotypically characterized. Then, experimental ataxia was induced in 20 male adult rats by a single injection of 3-AP and bilateral DPSC transplantation was performed 3 days after 3-AP administration, followed by stereological analysis of cerebellar layers along with assessment of motor skills and inflammatory response. The findings showed that transplantation of DPSCs in a 3-AP model of ataxia ameliorated motor coordination and muscle activity, increased cerebellar volumes of molecular and granular layers plus white matter, reduced the levels of inflammatory cytokines and thwarted the degeneration of Purkinje cells against 3-AP toxicity. Taken together, human DPSCs could be considered as a suitable candidate for CRT-based therapies with a specific focus on CA.
小脑共济失调 (CA) 包括一系列以小脑退化为特征的神经退行性疾病。细胞替代疗法 (CRT) 为与中枢神经系统 (CNS) 相关的疾病提供了一种潜在的治疗方法。本研究旨在评估牙髓干细胞 (DPSC) 移植对 3-乙酰吡啶 (3-AP) 诱导的 CA 大鼠模型的神经修复/保护作用，3-AP 是一种神经毒素。首先，提取、培养并表型鉴定人牙髓干细胞。然后，通过单次注射 3-AP 在 20 只雄性成年大鼠中诱导实验性共济失调，并在 3-AP 给药后 3 天进行双侧 DPSC 移植，随后对小脑层进行立体学分析，评估运动技能和炎症反应。研究结果表明，在 3-AP 诱导的共济失调模型中移植 DPSCs 可改善运动协调和肌肉活动，增加分子层和颗粒层以及白质的小脑体积，降低炎症细胞因子水平，并阻止浦肯野细胞对 3-AP 毒性的退化。综上所述，人牙髓干细胞可被视为基于 CRT 的治疗方法的合适候选物，特别针对 CA。
