CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Exosomes to control glioblastoma multiforme: Investigating the effects of mesenchymal stem cell-derived exosomes on C6 cells in vitro.
Exosomes to control glioblastoma multiforme: Investigating the effects of mesenchymal stem cell-derived exosomes on C6 cells in vitro.
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多形性胶质母细胞瘤(GBM)是一种常见、侵袭性强、生长迅速的中枢神经系统肿瘤,目前尚无有效治疗方法。尽管干细胞疗法在体外已显示出令人鼓舞的成果,但血脑屏障(BBB)一直是临床成功的主要障碍。为克服这一挑战,外泌体在众多研究中被作为有吸引力的药物递送载体,因为它们足够小,能够进入BBB。
此外,外泌体的特征和组成直接由亲本细胞决定,这些可遗传的特性影响其细胞相互作用。本文聚焦于外泌体作为干细胞疗法的替代方案来调节胶质瘤细胞活性。通过超速离心法从大鼠骨髓间充质干细胞(rBMMSCs)中分离外泌体,然后通过western blot、动态光散射、扫描电子显微镜和透射电子显微镜进行表征。接下来,将不同浓度的外泌体与C6细胞孵育,并在体外评估其在不同时间点的效果。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴化物和Annexin/Pi检测结果证实,分离的外泌体主要通过凋亡导致细胞死亡,并且观察到外泌体浓度与其细胞毒性之间呈线性相关。随后,划痕试验、集落形成试验和Transwell试验证实了外泌体对C6细胞迁移和侵袭行为的显著影响。这是首次将rBMMSC来源的外泌体作为GBM的单一治疗,而非与其他治疗联合使用或作为药物载体。
Glioblastoma multiforme (GBM) is a common, aggressive, fast-growing tumor of the central nervous system that currently has no effective treatment. Although stem cell therapy has shown promising in vitro achievements, the blood-brain barrier (BBB) has always been a major hurdle to clinical success. To overcome this challenge, exosomes have been targeted as attractive drug delivery agents in numerous studies since they are small enough to enter the BBB.
Furthermore, exosomes' characteristics and compositions are directly determined by the parent cell and these heritable traits affect their cell interactions. This article focuses on exosomes as an alternative to stem cell therapy to regulate glioma cell activity. Exosomes were isolated from rat bone marrow mesenchymal stem cells (rBMMSCs) by ultracentrifugation method and then characterized via western blot, dynamic light scattering, scanning, and transmission electron microscopy. Next, various concentrations of the exosomes were incubated with C6 cells and their effects at different time points were evaluated in vitro.
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Annexin/Pi assay results confirmed that the isolated exosomes cause cell death mostly through apoptosis, and a linear correlation was observed between exosomes' concentration and their cytotoxicity.
Following that, the scratch test, colony formation test, and Transwell assay confirmed exosomes' significant impact on the migration and invasion behavior of C6 cells. For the first time, rBMMSC-derived exosomes have been used as a single treatment for GBM rather than in combination with other treatments or as a pharmaceutical carrier.
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