Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Cancer Med. 2022 Oct;11(19):3687-3699. doi: 10.1002/cam4.4745. Epub 2022 Apr 20.
Exosomes are essential mediators of intercellular communication as they transport proteins and RNAs between cells. Owing to their tumor-targeting capacity, immune compatibility, low toxicity, and long half-life, mesenchymal stem cell-derived exosomes have great potential for the development of novel antitumor strategies. In this context, the role of exosomes produced by adipose-derived mesenchymal stem cells (ADSCs) for the treatment of bladder cancer (BC) remains unclear. Here, we investigated the use of ADSCs as a source of therapeutic exosomes, as well as their efficacy in delivering the tumor suppressor miR-138-5p in BC.
ADSCs stably expressing miR-138-5p were established using Lentivirus infection, and ADSC-derived miR-138-5p exosomes (Exo-miR-138-5p) were isolated from the cell culture medium. The effect of Exo-miR-138-5p on BC cell migration, invasion, and proliferation was evaluated in vitro using wound healing, transwell invasion, and proliferation assays. The in vivo effect of Exo-miR-138-5p was investigated using a subcutaneous xenograft mouse model.
Exo-miR-138-5p prevented the migration, invasion, and proliferation of BC cells in vitro. Moreover, ADSC-derived exosomes could penetrate tumor tissues and successfully deliver miR-138-5p to suppress the growth of xenograft tumors in vivo.
The present results reveal that ADSC-derived exosomes are an effective delivery vehicle for small molecule drugs in vivo, and exosome-delivered miR-138-5p is a promising therapeutic agent for BC treatment.
外泌体是细胞间通讯的重要介质,因为它们在细胞之间运输蛋白质和 RNA。由于其具有肿瘤靶向能力、免疫相容性、低毒性和长半衰期,间充质干细胞衍生的外泌体在开发新型抗肿瘤策略方面具有巨大潜力。在这种情况下,脂肪来源的间充质干细胞 (ADSC) 产生的外泌体在膀胱癌 (BC) 治疗中的作用尚不清楚。在这里,我们研究了将 ADSC 用作治疗性外泌体的来源,以及它们在递送肿瘤抑制 miR-138-5p 方面在 BC 中的功效。
使用慢病毒感染建立稳定表达 miR-138-5p 的 ADSC,从细胞培养上清液中分离 ADSC 衍生的 miR-138-5p 外泌体 (Exo-miR-138-5p)。使用划痕愈合、Transwell 侵袭和增殖测定体外评估 Exo-miR-138-5p 对 BC 细胞迁移、侵袭和增殖的影响。使用皮下异种移植小鼠模型研究 Exo-miR-138-5p 的体内作用。
Exo-miR-138-5p 可防止 BC 细胞在体外迁移、侵袭和增殖。此外,ADSC 衍生的外泌体可以穿透肿瘤组织,并成功地将 miR-138-5p 递送至体内抑制异种移植肿瘤的生长。
本研究结果表明,ADSC 衍生的外泌体是体内小分子药物的有效递送载体,外泌体递送的 miR-138-5p 是治疗 BC 的有前途的治疗剂。