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PCL/gelatin scaffolds and beta‐boswellic acid synergistically increase the efficiency of CGR8 stem cells differentiation into dopaminergic neuron: A new paradigm of Parkinson's disease cell therapy
Journal of Biomedical Materials Research Part A ( IF 3.9 ) Pub Date : 2020-06-25 , DOI: 10.1002/jbm.a.37040
Hamed Kheradmand 1 , Hamideh Babaloo 2 , Yasaman Vojgani 3, 4 , Sasan Mirzakhanlouei 5 , Neda Bayat 6
Affiliation  

Parkinson's disease is a progressive degenerative disorder in the central nervous system, which is distinguished by the death of dopamine‐producing nerve cells. Levodopa, a dopamine precursor drug, is the current standard of care of symptomatic treatment for Parkinson's disease. However, the long‐term use of the drug is associated with the development of motor fluctuations and dyskinesias. Cellular therapies aim to deploy fetal dopaminergic neurons as a means to replace the missing dopamine‐producing cells. The present study aims to study the impact of beta‐boswellic acid (BBA) coupled with poly ε‐caprolactone (PCL)/gelatin scaffolds on the dopaminergic differentiation course of CGR8 embryonic stem cells (ESCs). For this purpose, CGR8 ESCs were cultured on PCL/gelatin scaffolds and a five‐step protocol was employed to be promoted the neural differentiation of CGR8 ESCs. Gene expression analysis by real‐time qPCR demonstrated that PCL/gelatin scaffolds along with BBA treatment impose synergistic effects on the derivation of dopaminergic‐like cells from CGR8 ESCs. Reverse‐phase high‐performance liquid chromatography confirmed the functionality of the derived neurons by demonstrating the efficient secretion of dopamine in response to stimuli. Our results suggested that the generation of functional dopaminergic‐like cells from CGR8 ESCs was increased and supported by PCL/gelatin scaffolds and BBA treatment can heighten the efficiency. The result of this study may open insight into Parkinson's disease cell therapy and provide future directions for tissue engineering aimed at the treatment of Parkinson's disease.

中文翻译:

PCL/明胶支架和β-乳香酸协同提高CGR8干细胞分化为多巴胺能神经元的效率:帕金森病细胞治疗的新范式

帕金森病是一种中枢神经系统的进行性退行性疾病,其特征是产生多巴胺的神经细胞死亡。左旋多巴是一种多巴胺前体药物,是目前帕金森病对症治疗的护理标准。然而,长期使用该药物与运动波动和运动障碍的发展有关。细胞疗法旨在部署胎儿多巴胺能神经元作为替代缺失的多巴胺产生细胞的手段。本研究旨在研究β-乳香酸(BBA)与聚ε-己内酯(PCL)/明胶支架对CGR8胚胎干细胞(ESC)多巴胺能分化过程的影响。以此目的,CGR8 ESC 在 PCL/明胶支架上培养,采用五步法促进 CGR8 ESC 的神经分化。通过实时 qPCR 进行的基因表达分析表明,PCL/明胶支架与 BBA 处理对从 CGR8 ESC 衍生多巴胺样细胞产生协同作用。反相高效液相色谱通过证明多巴胺响应刺激的有效分泌来证实衍生神经元的功能。我们的结果表明,PCL/明胶支架和 BBA 处理可以增加和支持 CGR8 ESC 产生功能性多巴胺能样细胞。这项研究的结果可能会打开对帕金森病的了解
更新日期:2020-06-25
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