Guo Xing Rong, Hu Qin Yong, Yuan Ya Hong, Tang Xiang Jun, Yang Zhuo Shun, Zou Dan Dan, Bian Liu Jiao, Dai Long Jun, Li Dong Sheng
Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Oncol Lett. 2016 Apr;11(4):2733-2740. doi: 10.3892/ol.2016.4297. Epub 2016 Mar 1.
Mesenchymal stem cells (MSCs) have been considered to have potential as ideal carriers for the delivery of anticancer agents since the capacity for tumor-oriented migration and integration was identified. In contrast to DNA-based vectors, mRNA synthesized may be readily transfected and is mutagenesis-free. The present study was performed in order to investigate the effects of phosphatase and tensin homolog (PTEN) mRNA-engineered MSCs on human glioma U251 cells under indirect co-culture conditions. PTEN-bearing mRNA was generated by transcription and was transfected into MSCs. The expression of PTEN in transfected MSCs was detected by immunoblotting, and the migration ability of MSCs following PTEN-bearing mRNA transfection was verified using Transwell co-cultures. The indirect co-culture was used to determine the effects of PTEN-engineered MSCs on the viability of U251 glioma cells by luminescence and fluorescence microscopy. The synthesized PTEN mRNA was expressed in MSCs, and the expression was highest at 24 h subsequent to transfection. An enhanced migration rate was observed in MSCs transfected with PTEN mRNA compared with non-transfected MSCs (P<0.05). A significant inhibition of U251 cells was observed when the cells were cultured with conditioned medium from PTEN mRNA-engineered MSCs (P<0.05). The results suggested that anticancer gene-bearing mRNA synthesized is capable of being applied to a MSC-mediated anticancer strategy for the treatment of glioblastoma patients.
自从间充质干细胞（MSCs）被发现具有肿瘤趋向性迁移和整合能力以来，它们就被认为有潜力成为递送抗癌药物的理想载体。与基于DNA的载体不同，合成的mRNA易于转染且无致突变性。本研究旨在探讨在间接共培养条件下，磷酸酶和张力蛋白同源物（PTEN）mRNA工程化的MSCs对人胶质瘤U251细胞的影响。通过转录产生携带PTEN的mRNA，并将其转染到MSCs中。通过免疫印迹检测转染的MSCs中PTEN 的表达，并使用Transwell共培养验证携带PTEN的mRNA转染后MSCs的迁移能力。采用间接共培养，通过发光和荧光显微镜确定PTEN工程化的MSCs对U251胶质瘤细胞活力的影响。合成的PTEN mRNA在MSCs中表达，转染后24小时表达最高。与未转染的MSCs相比，转染PTEN mRNA的MSCs迁移率增加（P<0.05）。当U251细胞与PTEN mRNA工程化的MSCs的条件培养基一起培养时，观察到对U251细胞有显著抑制作用（P<0.05）。结果表明，合成的携带抗癌基因的mRNA能够应用于MSCs介导的抗癌策略，用于治疗胶质母细胞瘤患者。
