Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, No.246 Xuefu Road, Nangang District, Harbin, 150086, Heilongjiang, China.
Department of Biochemistry and Molecular Biology, Harbin Medical University, No.157 Baojian Road, Nangang District, Harbin, 150086, Heilongjiang, China.
Stem Cell Res Ther. 2023 Feb 13;14(1):25. doi: 10.1186/s13287-023-03251-5.
Hair follicle stem cells (HFSCs) are considered as a promising cell type in the stem cell transplantation treatment of neurological diseases because of their rich sources, easy access, and the same ectoderm source as the nervous system. Hepatocyte growth factor (HGF) is a pleiotropic cytokine that shows neuroprotective function in ischemic stroke. Here we assessed the therapeutic effects of HFSCs on ischemic stroke injury and the synthetic effect of HGF along with HFSCs.
Rat HFSCs were intravenously transplanted into a middle cerebral artery ischemia/reperfusion (I/R) rat model. Neurological scoring and TTC staining were performed to assess the benefits of HFSC transplantation. Inflammatory cytokines, blood-brain barrier integrity and angiogenesis within penumbra were estimated by Western blot and immunohistochemistry. The differentiation of HFSCs was detected by immunofluorescence method 2 weeks after transplantation.
HFSC transplantation could significantly inhibit the activation of microglia, improve the integrity of blood-brain barrier and reduce brain edema. Moreover, the number of surviving neurons and microvessels density in the penumbra were upregulated by HFSC transplantation, leading to better neurological score. The combination of HFSCs and HGF could significantly improve the therapeutic benefit.
Our results indicate for the first time that HGF modified HFSCs can reduce I/R injury and promote the neurological recovery by inhibiting inflammatory response, protecting blood-brain barrier and promoting angiogenesis.
毛囊干细胞（HFSCs）因其来源丰富、易于获取且与神经系统具有相同的外胚层来源，被认为是神经疾病干细胞移植治疗中有前途的细胞类型。肝细胞生长因子（HGF）是一种多效细胞因子，在缺血性中风中显示出神经保护作用。在这里，我们评估了 HFSCs 对缺血性中风损伤的治疗效果以及 HGF 与 HFSCs 联合的合成效果。
将大鼠 HFSCs 静脉移植到大脑中动脉缺血/再灌注（I/R）大鼠模型中。通过神经学评分和 TTC 染色评估 HFSC 移植的益处。通过 Western blot 和免疫组织化学评估缺血半影区的炎症细胞因子、血脑屏障完整性和血管生成。移植后 2 周通过免疫荧光法检测 HFSCs 的分化。
HFSC 移植可显著抑制小胶质细胞的激活，改善血脑屏障的完整性并减少脑水肿。此外，HFSC 移植可增加存活神经元的数量和缺血半影区微血管密度，从而改善神经学评分。HFSCs 和 HGF 的联合应用可显著提高治疗效果。
我们的研究结果首次表明，HGF 修饰的 HFSCs 通过抑制炎症反应、保护血脑屏障和促进血管生成，可减轻 I/R 损伤并促进神经功能恢复。
