Saeidikhoo Sara, Ezi Samira, Khatmi Aysan, Aghajanpour Fakhroddin, Soltani Reza, Abdollahifar Mohammad Amin, Jahanian Ali, Aliaghaei Abbas
Neuroscience Lab, Department of Cell Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Mol Neurosci. 2020 Jul;70(7):1153-1163. doi: 10.1007/s12031-020-01522-x. Epub 2020 Mar 12.
To date, no certain cure has been found for patients with degenerative cerebellar disease. In this trial, we examined the in vivo and in vitro neuroprotective effects of Sertoli cells (SCs) on alleviating the symptoms of cerebellar ataxia. Testicular cells from an immature male rat were isolated and characterized by immunocytochemical analysis for somatic cell markers (anti-Mullerian hormone, vimentin). The protein assessment had already confirmed the expression of neurotrophic factors of glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial factor (VEGF). In vitro neuroprotective impact of SCs was determined after exposing PC12 cells to Sertoli cell-conditioned media (SC-CM) and HO, simultaneously. Afterwards, ataxia rat models were induced by a single dose of 3-AP (3-acetylpyridin), and 3 days later, SCs were bilaterally implanted. Motor and neuromuscular activity test were conducted following SC transplantation. Finally, immunohistochemistry against RIPK3 and Iba-1 was done in our generation. The in vivo results revealed substantial improvement in neuromuscular response, while ataxia group exhibited aggravated condition over a 28-day period. Our results suggested enhanced motor function and behavioral characteristics due to the ability of SCs to suppress necroptosis and consequently extend cell survival. Nevertheless, more studies are required to affirm the therapeutic impacts of SC transplantation in human cerebellar ataxia. In vitro data indicated cell viability was increased as a result of SC-CM with a significant reduction in ROS.
迄今为止,尚未发现针对退行性小脑疾病患者的确切治愈方法。在本试验中,我们研究了支持细胞(SCs)在体内和体外对减轻小脑共济失调症状的神经保护作用。从未成熟雄性大鼠分离出睾丸细胞,并通过体细胞标志物(抗苗勒管激素、波形蛋白)的免疫细胞化学分析进行表征。蛋白质评估已经证实了胶质细胞源性神经营养因子(GDNF)和血管内皮生长因子(VEGF)等神经营养因子的表达。在将PC12细胞同时暴露于支持细胞条件培养基(SC-CM)和HO后,确定了SCs的体外神经保护作用。之后,通过单剂量3-AP(3-乙酰吡啶)诱导共济失调大鼠模型,3天后双侧植入SCs。在SCs移植后进行运动和神经肌肉活动测试。最后,对我们这一代进行了针对RIPK3和Iba-1的免疫组织化学检测。体内结果显示神经肌肉反应有显著改善,而共济失调组在28天内病情加重。我们的结果表明,由于SCs具有抑制坏死性凋亡并因此延长细胞存活的能力,运动功能和行为特征得到了增强。然而,需要更多的研究来证实SCs移植对人类小脑共济失调的治疗效果。体外数据表明,SC-CM可提高细胞活力,并显著降低活性氧水平。