Stomatologic Hospital & College, Anhui Medical University, Key Lab of Oral Diseases Research of Anhui Province, 69 Meishan Road, Shushan District, Hefei, Anhui, 230001, China.
Department of Rehabilitation Medicine, Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Shushan District, Hefei, Anhui, 230061, China.
Tissue Cell. 2021 Apr;69:101482. doi: 10.1016/j.tice.2020.101482. Epub 2020 Dec 25.
Ischemia or hemorrhagic stroke is one of the leading causes of death and permanent disability in the worldwide population. As a consequence of the potential increasing in stroke, stem cell therapy is currently an area of intense focus. However, there are less data available regarding the promotion of healing efficacy after stroke. The present study aimed to investigate whether the cytokine interleukin-17A (IL-17A) could have a role in promoting the neuronal differentiation of mesenchymal stem cells (MSCs) and to investigate the associated molecular mechanism. Firstly, different concentration of IL-17A at range from 5-40 ng/mL was applied to stimulate bone marrow MSCs (BMSCs) during the course of neurogenic differentiation. Then reverse transcription-PCR, histological analyses and immunofluorescence assays were used to determine the optimum concentration of IL-17A in promoting the neuronal differentiation of BMSCs, which was 20 ng/mL. Mechanistically, Wnt signaling pathway was activated and Notch signaling pathway was suppressed. In addition, there were antergic effect of these two signaling pathways modulating the neurogenic differentiation of BMSCs induced by IL-17A. The present study demonstrated the potential role of IL-17A-based BMSCs strategy for promoting neuronal differentiation in vitro. However, the treatment efficacy could be considerably confirmed in animals with ischemia stroke. Therefore, a more sophisticated strategy that addresses the complicated treatment associated with stroke is needed.
缺血性或出血性中风是全球人口死亡和永久残疾的主要原因之一。由于中风的潜在发病率增加,干细胞疗法目前是一个备受关注的领域。然而,关于中风后促进愈合效果的数据较少。本研究旨在探讨细胞因子白细胞介素-17A(IL-17A)是否在促进间充质干细胞(MSCs)的神经元分化中发挥作用,并研究其相关的分子机制。首先,在神经发生分化过程中,将不同浓度的 IL-17A(范围为 5-40ng/ml)应用于骨髓间充质干细胞(BMSCs)。然后,通过逆转录-PCR、组织学分析和免疫荧光检测,确定促进 BMSCs 神经元分化的最佳 IL-17A 浓度为 20ng/ml。从机制上讲,Wnt 信号通路被激活,Notch 信号通路被抑制。此外,这两种信号通路的协同作用调节了 IL-17A 诱导的 BMSCs 神经发生分化。本研究表明,基于 IL-17A 的 BMSCs 策略在体外促进神经元分化具有潜在作用。然而,在缺血性中风动物中,其治疗效果可以得到更充分的证实。因此,需要一种更复杂的策略来解决与中风相关的复杂治疗问题。