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Implantation of glial cell line-derived neurotrophic factor-expressing adipose tissue-derived stromal cells in a rat Parkinson's disease model.
Neurological Research ( IF 1.7 ) Pub Date : 2020-06-21 , DOI: 10.1080/01616412.2020.1783473
Rong Xu 1 , Julei Wu 2 , Liqin Lang 1 , Jie Hu 1 , Hailiang Tang 1 , Juefeng Xu 2 , Bing Sun 1
Affiliation  

In previous studies, the effects of glial cell line-derived neurotrophic factor (GDNF) expressing adipose tissue-derived stromal cells (ADSCs) on Parkinson’s disease (PD) models have been studied but have not been elucidated. The present study aims to investigate this phenomenon and trace their differentiation in vivo. In our study, ADSCs were harvested from adult Sprague-Dawley rats, then genetically modified into GDNF-expressing system by lentivirus. The secretion of GDNF from the transduced cells was titrated by enzyme-linked immunosorbent assay (ELISA). Cellular differentiation in vitro was observed after induction. To examine survival and differentiation in vivo, they were injected into the striatum of 6-hydroxydopamine-lesioned rats, whose apomorphine-induced rotations were examined 2, 7, 14 and 21d after grafting. It’s found that GDNF-expressing ADSCs can differentiate into neuron-like cells in vitro. Moreover, engrafted GDNF-expressing ADSCs survived at least 90 days post-grafting and differentiated into dopaminergic neuron-like cells. Most importantly, these cells drastically improved the clinical symptoms of PD rats. In conclusion, ADSCs can be efficiently engineered by lentivirus system and deliver a therapeutic level of the transgene to target tissues. GDNF-ADSCs can improve behavior phenotype in the rat PD model. Moreover, ADSCs is a more readily available source of dopaminergic neurons, though a more effective procedure needs to be developed to enrich the number of differentiation.



中文翻译:

在大鼠帕金森氏病模型中植入源自神经胶质细胞系的表达神经营养因子的脂肪基质细胞。

在以前的研究中,已经研究了表达神经胶质细胞系的神经营养因子(GDNF)的脂肪组织来源的基质细胞(ADSC)对帕金森氏病(PD)模型的影响,但尚未阐明。本研究旨在调查这种现象并追踪它们在体内的分化。在我们的研究中,从成年Sprague-Dawley大鼠中收获ADSC,然后通过慢病毒将其遗传修饰成GDNF表达系统。通过酶联免疫吸附测定(ELISA)来滴定转导细胞中GDNF的分泌。诱导后观察到体外细胞分化。检查体内存活和分化,将它们注射到6-羟基多巴胺损伤大鼠的纹状体中,在移植后第2、7、14和21天检查其阿扑吗啡诱导的旋转。发现表达GDNF的ADSCs可以在体外分化为神经元样细胞。此外,移植的表达GDNF的ADSC在移植后至少存活90天,并分化为多巴胺能神经元样细胞。最重要的是,这些细胞大大改善了PD大鼠的临床症状。总之,慢病毒系统可以有效地改造ADSC,并将治疗水平的转基因传递给靶组织。GDNF-ADSCs可以改善大鼠PD模型的行为表型。此外,ADSCs是更容易获得的多巴胺能神经元来源,尽管需要开发更有效的程序来丰富分化数量。

更新日期:2020-08-05
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