Ningxia Medical University, Yinchuan, 750004, China; Department of Neurosurgery, The First Hospital of Qiqihar, Qiqihar, 161005, China.
Department of Neurosurgery, The First Hospital of Qiqihar, Qiqihar, 161005, China.
Biochem Biophys Res Commun. 2022 Dec 25;636(Pt 1):170-177. doi: 10.1016/j.bbrc.2022.10.013. Epub 2022 Oct 5.
NSCs play an essential role in the regeneration process of the central nervous system. However, due to the influence of the harsh pathological microenvironment, the viability of neural stem cells is limited, and the therapeutic effect needs improvement. Previous studies have found that stem cells overexpressing ciliary neurotrophic factor (CNTF) have apparent therapeutic effects on remyelination, but the specific mechanism of action still needs to be further explored. We found that astrocytes, the most numerous groups in the CNS, exhibited a pathological role in the experimental autoimmune encephalomyelitis model, but after stimulation with CNTF-NSCs, a phenotypic switch occurred and induced the neurotrophic factor cardiotrophin-like cytokine 1 (Clcf1) production. Mechanistically, Clcf1 can significantly promote the differentiation of oligodendrocyte precursor cells (OPCs), and the advanced effect can attenuate by the Clcf1 antibody. Therefore, this study was conducted to investigate the pathway by which CNTF-NSCs exert their therapeutic effects by affecting astrocytes. It is expected to identify a potential therapeutic factor, Clcf1, for the treatment of demyelinating diseases.
神经干细胞在中枢神经系统的再生过程中起着至关重要的作用。然而，由于恶劣的病理微环境的影响，神经干细胞的存活能力有限，治疗效果需要提高。先前的研究发现，过表达睫状神经营养因子（CNTF）的干细胞对髓鞘再生有明显的治疗作用，但具体的作用机制仍需进一步探讨。我们发现，星形胶质细胞是中枢神经系统中数量最多的细胞群，在实验性自身免疫性脑脊髓炎模型中表现出病理性作用，但在受到 CNTF-NSC 刺激后，发生表型转换，并诱导神经营养因子心脏营养素样细胞因子 1（Clcf1）的产生。从机制上讲，Clcf1 可显著促进少突胶质前体细胞（OPC）的分化，而 Clcf1 抗体可减弱其促进作用。因此，本研究旨在探讨 CNTF-NSC 通过影响星形胶质细胞发挥治疗作用的途径。有望鉴定出一种潜在的治疗因子 Clcf1，用于治疗脱髓鞘疾病。
