依达拉奉对大鼠多发性硬化症中人类脂肪来源干细胞向少突胶质细胞分化的影响评估

Evaluation of Edaravone effects on the differentiation of human adipose derived stem cells into oligodendrocyte cells in multiple sclerosis disease in rats.

作者信息

Bakhtiari Mohammad, Ghasemi Nazem, Salehi Hossein, Amirpour Noushin, Kazemi Mohammad, Mardani Mohammad

机构信息

Department of Anatomical Science, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Life Sci. 2021 Oct 1;282:119812. doi: 10.1016/j.lfs.2021.119812. Epub 2021 Jul 12.

DOI:10.1016/j.lfs.2021.119812

PMID:34265362

Abstract

AIMS

Among all the treatments for Multiple Sclerosis, stem cell transplantation, such as ADSCs, has attracted a great deal of scientific attention. On the other hand, Edaravone, as an antioxidant component, in combination with stem cells, could increase the survival and differentiation potential of stem cells.

MAIN METHODS

42 rats were divided into: Control, Cuprizone (CPZ), Sham, Edaravone (Ed), hADSCs, and Ed/hADSCs groups. Following induction of cuprizone, induced MS model, behavioral tests were designed to evaluate motor function during. Luxal fast blue staining was done to measure the level of demyelination and remyelination. Immunofluorescent staining was used to evaluate the amount of MBP, OLIG2, and MOG proteins. The mRNA levels of human MBP, MOG, and OLIG2 and rat Mbp, Mog, and Olig2 were determined via RT-PCR.

KEY FINDINGS

Flow cytometry analysis exhibited that the extracted cells were positive for CD73 (93.8 ± 3%) and CD105 (91.6 ± 3%), yet negative for CD45 (2.06 ± 0.5%). Behavioral tests, unveiled a significant improvement in the Ed (P < 0.001), hADSCs (P < 0.001), and Ed/hADSCs (P < 0.001) groups compared to the others. In the Ed/hADSCs group, the myelin density was significantly higher than that in the Ed treated and hADSCs treated groups (P < 0.01). Edaravone and hADSCs increased the expression of Mbp, Mog, and Olig2 genes in the cuprizone rat models. Moreover, significant differences were seen between the Ed treated and hADSCs treated groups and the Ed/hADSCs group (P < 0.05 for Mbp and Olig2 and P < 0.01 for Mog).

SIGNIFICANCE

Edaravone in combination with hADSCs reduced demyelination and increased oligodendrogenesis in the cuprizone rat models.

摘要

目的

在多发性硬化症的所有治疗方法中，干细胞移植，如脂肪来源干细胞（ADSCs），已引起了大量科学关注。另一方面，依达拉奉作为一种抗氧化成分，与干细胞联合使用，可提高干细胞的存活率和分化潜能。

主要方法

将42只大鼠分为：对照组、铜唑酮（CPZ）组、假手术组、依达拉奉（Ed）组、人脂肪来源干细胞（hADSCs）组和依达拉奉/hADSCs组。诱导铜唑酮后，建立诱导性多发性硬化症模型，设计行为测试以评估期间的运动功能。进行Luxal固蓝染色以测量脱髓鞘和再髓鞘化水平。使用免疫荧光染色评估髓鞘碱性蛋白（MBP）、少突胶质细胞转录因子2（OLIG2）和髓鞘少突胶质细胞糖蛋白（MOG）蛋白的含量。通过逆转录聚合酶链反应（RT-PCR）测定人MBP、MOG和OLIG2以及大鼠Mbp、Mog和Olig2的mRNA水平。

主要发现

流式细胞术分析显示，提取的细胞CD73呈阳性（93.8±3%），CD105呈阳性（91.6±3%），而CD45呈阴性（2.06±0.5%）。行为测试表明，与其他组相比，Ed组（P<0.001）、hADSCs组（P<0.001）和Ed/hADSCs组（P<0.001）有显著改善。在Ed/hADSCs组中，髓磷脂密度显著高于Ed治疗组和hADSCs治疗组（P<0.01）。依达拉奉和hADSCs增加了铜唑酮大鼠模型中Mbp、Mog和Olig2基因的表达。此外，Ed治疗组和hADSCs治疗组与Ed/hADSCs组之间存在显著差异（Mbp和Olig2为P<0.05，Mog为P<0.01）。