Wang Jiayin, Xia Jinchao, Zhang Feng, Shi Yejie, Wu Yun, Pu Hongjian, Liou Anthony K F, Leak Rehana K, Yu Xinguang, Chen Ling, Chen Jun
1] Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China [2] Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
1] Cerebrovascular Center, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou 450003, China [2] Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Sci Rep. 2015 Apr 10;5:9621. doi: 10.1038/srep09621.
Galectin-1 (gal-1), a special lectin with high affinity to β-galactosides, is implicated in protection against ischemic brain injury. The present study investigated transplantation of gal-1-secreting neural stem cell (s-NSC) into ischemic brains and identified the mechanisms underlying protection. To accomplish this goal, secretory gal-1 was stably overexpressed in NE-4C neural stem cells. Transient cerebral ischemia was induced in mice by middle cerebral artery occlusion for 60 minutes and s-NSCs were injected into the striatum and cortex within 2 hours post-ischemia. Brain infarct volume and neurological performance were assessed up to 28 days post-ischemia. s-NSC transplantation reduced infarct volume, improved sensorimotor and cognitive functions, and provided more robust neuroprotection than non-engineered NSCs or gal-1-overexpressing (but non-secreting) NSCs. White matter injury was also ameliorated in s-NSC-treated stroke mice. Gal-1 modulated microglial function in vitro, by attenuating secretion of pro-inflammatory cytokines (TNF-α and nitric oxide) in response to LPS stimulation and enhancing production of anti-inflammatory cytokines (IL-10 and TGF-β). Gal-1 also shifted microglia/macrophage polarization toward the beneficial M2 phenotype in vivo by reducing CD16 expression and increasing CD206 expression. In sum, s-NSC transplantation confers robust neuroprotection against cerebral ischemia, probably by alleviating white matter injury and modulating microglial/macrophage function.
半乳糖凝集素-1（gal-1）是一种对β-半乳糖苷具有高亲和力的特殊凝集素，与缺血性脑损伤的保护作用有关。本研究调查了分泌gal-1的神经干细胞（s-NSC）移植到缺血性脑内的情况，并确定了其保护作用的潜在机制。为实现这一目标，在NE-4C神经干细胞中稳定过表达分泌型gal-1。通过大脑中动脉闭塞60分钟诱导小鼠短暂性脑缺血，并在缺血后2小时内将s-NSC注入纹状体和皮质。在缺血后28天内评估脑梗死体积和神经功能。与未改造的神经干细胞或过表达（但不分泌）gal-1的神经干细胞相比，s-NSC移植减少了梗死体积，改善了感觉运动和认知功能，并提供了更强有力的神经保护作用。在接受s-NSC治疗的中风小鼠中，白质损伤也得到了改善。Gal-1在体外调节小胶质细胞功能，通过减弱对脂多糖刺激的促炎细胞因子（TNF-α和一氧化氮）分泌，并增强抗炎细胞因子（IL-10和TGF-β）的产生。Gal-1还通过降低CD16表达和增加CD206表达，在体内使小胶质细胞/巨噬细胞极化向有益的M2表型转变。总之，s-NSC移植对脑缺血具有强大的神经保护作用，可能是通过减轻白质损伤和调节小胶质细胞/巨噬细胞功能来实现的。
