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川芎嗪对人脐带间充质干细胞治疗脑卒中特性的剂量依赖性影响。

Dose-dependent effects of tetramethylpyrazine on the characteristics of human umbilical cord mesenchymal stem cells for stroke therapy.

机构信息

Department of Laboratory Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinease Medicine, Nanjing, Jiangsu, PR China.

Department of Laboratory Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinease Medicine, Nanjing, Jiangsu, PR China.

出版信息

Neurosci Lett. 2020 Mar 23;722:134797. doi: 10.1016/j.neulet.2020.134797. Epub 2020 Feb 14.

Abstract

Umbilical cord mesenchymal stem cells (ucMSCs) may serve as a new source for cell therapy in stroke patients; however, the poor efficiency of viability, migration, and differentiation limit the application of ucMSCs. This study determined the dose-dependent effects of tetramethylpyrazine (TMP) on the characteristics of ucMSCs in vitro. The effect on proliferation was determined with Cell Counting kit-8 assays. Cell migration was analyzed with Transwell assays and western blot analysis. Differentiation of ucMSCs was evaluated according to markers and the expression of relevant proteins and genes. Secretion capacity was detected by ELISA analysis. TMP protected ucMSCs against HO induced-oxidative damage but had no influence on ucMSC activity at a low concentration. Furthermore, ucMSC migration was improved by TMP via the SDF-1/CXCR4 axis. The observed effects were dose dependent. At a high dose, however, TMP induced the differentiation of ucMSCs into neuron-like cells that expressed neuron-specific markers. In addition, the secretion of cytokines was significantly increased by TMP. Therefore, TMP pre-treatment of ucMSCs may be an effective strategy to enhance the efficiency of ucMSC transplantation in stroke therapy.

摘要

脐带间充质干细胞(ucMSCs)可能成为脑卒中患者细胞治疗的新来源;然而,其活力、迁移和分化效率低下限制了 ucMSCs 的应用。本研究旨在确定川芎嗪(TMP)对体外 ucMSCs 特性的剂量依赖性影响。通过细胞计数试剂盒-8 测定法来确定增殖的效果。通过 Transwell 分析和 Western blot 分析来分析细胞迁移。根据标记物以及相关蛋白和基因的表达来评估 ucMSCs 的分化。通过 ELISA 分析检测分泌能力。TMP 可保护 ucMSCs 免受 HO 诱导的氧化损伤,但在低浓度时对 ucMSC 活性没有影响。此外,TMP 通过 SDF-1/CXCR4 轴促进 ucMSC 迁移。观察到的效果是剂量依赖性的。然而,在高剂量时,TMP 诱导 ucMSCs 分化为表达神经元特异性标志物的神经元样细胞。此外,TMP 显著增加细胞因子的分泌。因此,TMP 预处理 ucMSCs 可能是提高 ucMSC 移植在脑卒中治疗中效率的有效策略。

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