Wang Xiao-Jun, Xiang Bing-Yu, Ding Ya-Hui, Chen Lu, Zou Hai, Mou Xiao-Zhou, Xiang Charlie
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Department of Cardiology, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
Oncotarget. 2017 May 4;8(35):58309-58321. doi: 10.18632/oncotarget.17621. eCollection 2017 Aug 29.
Despite many advances in conventional treatment strategies, there is no effective treatment modality for malignant gliomas. Gene therapy may offer a promising option for gliomas and several gene therapy approaches have shown anti-tumor efficiency in previous studies. Mesenchymal stem cell-based gene therapies, in which stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential because of their innate homing ability. In this study, human menstrual blood-derived MSCs (MenSC), a novel type of multipotential MSCs displays tropism for human malignant glioma when used as a gene delivery vehicle for therapeutics. Secretable trimeric TRAIL (stTRAIL) contains the receptor-binding domain of TRAIL, a death ligand that induces apoptosis in tumor cells. To overexpress stTRAIL, MenSCs were infected with efficient adenoviral serotype 35 vectors that had no influence on its broad multipotency and low immunophenotype. The modified MenSCs served as an excellent local drug delivery system for tumor site-specific targeted delivery and demonstrated therapeutic efficacy in an animal xenografts tumor model of U-87 MG cells. The MenSC-stTRAIL cells induced antitumor effects by significantly increasing apoptosis ( < 0.05). It also significantly reduced tumor burden ( < 0.05). The results showed that the proliferation of tumor cells was significantly reduced ( < 0.05). The MenSC, as a cellular delivery vehicle has a wide potential therapeutic role, which includes the treatment of tumors.
尽管传统治疗策略取得了许多进展，但恶性胶质瘤仍没有有效的治疗方式。基因治疗可能为胶质瘤提供一个有前景的选择，并且几种基因治疗方法在先前的研究中已显示出抗肿瘤效果。基于间充质干细胞的基因治疗，即对干细胞进行基因工程改造以表达治疗分子，由于其固有的归巢能力而显示出巨大潜力。在本研究中，人月经血来源的间充质干细胞（MenSC），一种新型的多能间充质干细胞，当用作治疗药物的基因递送载体时，对人恶性胶质瘤表现出嗜性。可分泌的三聚体TRAIL（stTRAIL）包含TRAIL的受体结合域，TRAIL是一种可诱导肿瘤细胞凋亡的死亡配体。为了使stTRAIL过表达，用高效腺病毒35型载体感染MenSC，该载体对其广泛的多能性和低免疫表型没有影响。经修饰的MenSC作为一种出色的局部给药系统，用于肿瘤部位特异性靶向递送，并在U-87 MG细胞的动物异种移植肿瘤模型中显示出治疗效果。MenSC-stTRAIL细胞通过显著增加细胞凋亡诱导抗肿瘤作用（<0.05）。它还显著减轻了肿瘤负担（<0.05）。结果表明肿瘤细胞的增殖显著降低（<0.05）。MenSC作为一种细胞递送载体具有广泛的潜在治疗作用，包括肿瘤治疗。
