Yudintceva Natalia, Lomert Ekaterina, Mikhailova Natalia, Tolkunova Elena, Agadzhanian Nikol, Samochernych Konstantin, Multhoff Gabriele, Timin Grigoriy, Ryzhov Vyacheslav, Deriglazov Vladimir, Mazur Anton, Shevtsov Maxim
Institute of Cytology of the Russian Academy of Sciences (RAS), 194064 St. Petersburg, Russia.
Personalized Medicine Centre, Almazov National Medical Research Centre, Polenov Russian Scientific, Research Institute of Neurosurgery, 197341 St. Petersburg, Russia.
Biomedicines. 2021 Nov 1;9(11):1592. doi: 10.3390/biomedicines9111592.
Despite multimodal approaches for the treatment of multiforme glioblastoma (GBM) advances in outcome have been very modest indicating the necessity of novel diagnostic and therapeutic strategies. Currently, mesenchymal stem cells (MSCs) represent a promising platform for cell-based cancer therapies because of their tumor-tropism, low immunogenicity, easy accessibility, isolation procedure, and culturing. In the present study, we assessed the tumor-tropism and biodistribution of the superparamagnetic iron oxide nanoparticle (SPION)-labeled MSCs in the orthotopic model of C6 glioblastoma in Wistar rats. As shown in in vitro studies employing confocal microscopy, high-content quantitative image cytometer, and xCelligence system MSCs exhibit a high migratory capacity towards C6 glioblastoma cells. Intravenous administration of SPION-labeled MSCs in vivo resulted in intratumoral accumulation of the tagged cells in the tumor tissues that in turn significantly enhanced the contrast of the tumor when high-field magnetic resonance imaging was performed. Subsequent biodistribution studies employing highly sensitive nonlinear magnetic response measurements () supported by histological analysis confirm the retention of MSCs in the glioblastoma. In conclusion, MSCs due to their tumor-tropism could be employed as a drug-delivery platform for future theranostic approaches.
尽管多形性胶质母细胞瘤(GBM)的治疗采用了多模态方法,但治疗效果的进展非常有限,这表明需要新的诊断和治疗策略。目前,间充质干细胞(MSCs)因其肿瘤趋向性、低免疫原性、易于获取、分离程序和培养等特点,成为基于细胞的癌症治疗的一个有前景的平台。在本研究中,我们评估了超顺磁性氧化铁纳米颗粒(SPION)标记的MSCs在Wistar大鼠C6胶质母细胞瘤原位模型中的肿瘤趋向性和生物分布。如在使用共聚焦显微镜、高内涵定量图像细胞仪和xCelligence系统的体外研究中所示,MSCs对C6胶质母细胞瘤细胞具有高迁移能力。体内静脉注射SPION标记的MSCs导致标记细胞在肿瘤组织内瘤内积聚,进而在进行高场磁共振成像时显著增强了肿瘤的对比度。随后采用高灵敏度非线性磁响应测量()并辅以组织学分析的生物分布研究证实了MSCs在胶质母细胞瘤中的滞留。总之,由于MSCs的肿瘤趋向性,它们可作为未来治疗诊断方法的药物递送平台。