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Exosomes derived from TRAIL-engineered mesenchymal stem cells with effective anti-tumor activity in a mouse melanoma model

微泡 间充质干细胞 体内 外体 癌症研究 肿瘤坏死因子α 化学 干细胞 体外 细胞生物学 生物 免疫学 小RNA 生物化学 基因 生物技术
作者
Fazileh Hosseini Shamili,Houshang Rafatpanah Bayegi,Zahra Salmasi,Kayvan Sadri,Mahmoud Mahmoudi,Mahmoud Reza Kalantari,Mohammad Ramezani,Khalil Abnous
出处
期刊:International Journal of Pharmaceutics [Elsevier]
卷期号:549 (1-2): 218-229 被引量:70
标识
DOI:10.1016/j.ijpharm.2018.07.067
摘要

Exosomes are biological nano-sized vesicles (~30-200 nm in diameter) that are produced by a wide range of cells and play several roles in cell-cell communications. These vesicles contain membrane and cytoplasmic components of producing cells. Mesenchymal stem cells (MSCs) are the ideal producer of exosomes. The secreted vesicles from MSCs are promising biological vehicles for cell-free therapy in regenerative medicine, cancer therapy and targeted delivery of therapeutic agents to the tumor cells. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising member of the TNF family with selective effect on cancerous cells. Recent evidences showed that the membrane TRAIL-armed exosomes possess anti-tumor activity. However, the effect of in vivo administration of TRAIL-armed exosomes has not been reported so far. In the current study, mesenchymal stem cells expressing TRAIL/GFP proteins were prepared with the help of a non-viral vector based on polyethylenimine 25 kDa. Then, exosomes containing TRAIL protein (Exo-TRAIL) were isolated from the supernatant of genetically engineered MSCs and characterized. Antitumor activity of both MSC-derived exosomes and Exo-TRAIL was investigated in vitro and in vivo in three models. The results indicated that the co-injection of both Exo-TRAIL and tumor cells delayed the tumor appearance. Besides, the tumor volume/weight was efficiently decreased in tumor bearing mice. Moreover, it was shown that multi-dose injections of Exo-TRAIL reduced the tumor size while single dose treatment with Exo-TRAIL did not show significant anti-tumor activity. To conclude, these results suggested that MSC-derived Exo-TRAIL has a potential capacity for cancer treatment. [corrected].
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