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穿心莲内酯通过 Wnt/-Catenin 信号通路促进大鼠脂肪组织来源基质细胞的神经分化。

Andrographolide Promotes Neural Differentiation of Rat Adipose Tissue-Derived Stromal Cells through Wnt/-Catenin Signaling Pathway.

机构信息

Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

出版信息

Biomed Res Int. 2017;2017:4210867. doi: 10.1155/2017/4210867. Epub 2017 Sep 20.

Abstract

Adipose tissue-derived stromal cells (ADSCs) are a high-yield source of pluripotent stem cells for use in cell-based therapies. We explored the effect of andrographolide (ANDRO, one of the ingredients of the medicinal herb extract) on the neural differentiation of rat ADSCs and associated molecular mechanisms. We observed that rat ADSCs were small and spindle-shaped and expressed multiple stem cell markers including nestin. They were multipotent as evidenced by adipogenic, osteogenic, chondrogenic, and neural differentiation under appropriate conditions. The proportion of cells exhibiting neural-like morphology was higher, and neurites developed faster in the ANDRO group than in the control group in the same neural differentiation medium. Expression levels of the neural lineage markers MAP2, tau, GFAP, and -tubulin III were higher in the ANDRO group. ANDRO induced a concentration-dependent increase in Wnt/-catenin signaling as evidenced by the enhanced expression of nuclear -catenin and the inhibited form of GSK-3 (pSer9). Thus, this study shows for the first time how by enhancing the neural differentiation of ADSCs we expect that ANDRO pretreatment may increase the efficacy of adult stem cell transplantation in nervous system diseases, but more exploration is needed.

摘要

脂肪组织来源的基质细胞(ADSCs)是用于细胞治疗的多能干细胞的高产量来源。我们探讨了穿心莲内酯(ANDRO,草药提取物的一种成分)对大鼠 ADSCs 的神经分化的影响及其相关分子机制。我们观察到大鼠 ADSCs 呈小的梭形,表达多种干细胞标志物,包括巢蛋白。它们具有多能性,可在适当条件下分化为脂肪细胞、成骨细胞、软骨细胞和神经细胞。在相同的神经分化培养基中,ANDRO 组中表现出类神经形态的细胞比例更高,神经突的发育速度也比对照组更快。ANDRO 组中神经谱系标志物 MAP2、tau、GFAP 和 β-微管蛋白 III 的表达水平更高。ANDRO 诱导 Wnt/β-catenin 信号的浓度依赖性增加,表现为核β-catenin 的表达增强和 GSK-3(pSer9)的抑制形式。因此,这项研究首次表明,通过增强 ADSCs 的神经分化,我们期望 ANDRO 预处理可能会提高成年干细胞移植在神经系统疾病中的疗效,但需要进一步探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/427b/5632471/66982b088e04/BMRI2017-4210867.001.jpg

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