小型细胞外囊泡（sEV）含有各种微小RNA（miRNA），在肿瘤转移过程中发挥关键作用。虽然腹腔转移（PM）患者腹膜外泌体中miR-29b水平明显降低，但其作用尚未完全阐明。在本研究中，我们探讨了miR-29b的替代是否能影响小鼠模型中PM的发展。UE6E7T-12是一种人类骨髓来源的间充质干细胞（BMSCs），通过miR-29b整合重组慢病毒载体转染，以及使用超离心法从培养上清液中分离的sEV。与阴性对照相比，sEV中的miR-29b含量明显增加。经过TGF-β1处理后，人腹膜间皮细胞（HPMC）。E-钙黏蛋白和卡尔雷定的表达降低，vimentin和纤维连接蛋白的表达增加。然而，miR-29b丰富的sEV可完全抑制这些影响。sEV可将HPMC的增殖和迁移抑制15％（p <0.005，n = 6），70％（p <0.005，n = 6），并将NUGC-4和MKN45粘附到HPMC的抑制率分别降低90％（p <0.0001，n = 5）和77％（p <0.0001，n = 5）。通过使用小鼠BMSCs制备富含miR-29b的小鼠sEV，并在YTN16P（一种高度转移性胃癌细胞系的同种异体小鼠模型中进行了体内效果检验。每3天经腹腔（IP）转移这些sEV可显着降低YTN16P在肠系膜（p <0.05，n = 6）和网膜上PM的数量（P <0.05，n = 6）。BMSC来源的sEV是IP给予miR-29b的有用载体，可抑制胃癌PM的发展。本文受版权保护。保留所有权利。

Small extracellular vesicles (sEV) contain various microRNAs (miRNAs) and play crucial roles in the tumor metastatic process. Although miR-29b levels in peritoneal exosomes was markedly reduced in patients with peritoneal metastases (PM), their role has not been fully clarified. In this study, we asked if the replacement of miR-29b can affect the development of PM in murine model. UE6E7T-12, a human bone marrow derived mesenchymal stem cells (BMSCs), were transfected with miR-29b-integrating recombinant lenti-viral vector and sEV isolated from culture supernatants using ultracentrifugation. The sEV contained markedly increased amounts of miR-29b compared with negative controls. Treatment with TGF-β1 decreased the expression of E-cadherin and calretinin with increased expression of vimentin and fibronectin on human peritoneal mesothelial cells (HPMCs). However, the effects were totally abrogated by the adding miR-29b-rich sEV. The sEV inhibited proliferation and migration of HPMCs by 15% (p< 0.005, n=6), 70% (p< 0.005, n=6), and inhibited adhesion of NUGC-4 and MKN45 to HPMCs by 90 % (p< 0.0001, n=5) and 77% (p< 0.0001, n=5), respectively. MiR-29b-rich murine sEV were similarly obtained using mouse BMSCs and examined for in vivo effects with a syngeneic murine model using YTN16P, a highly metastatic clone of gastric cancer cell. Intraperitoneal (IP) transfer of the sEV for every 3 days markedly reduced the number of PM from YTN16P in the mesentery (p< 0.05, n=6) and the omentum (p< 0.05, n=6). BMSC-derived sEV are a useful carrier for IP administration of miR-29b which can suppress the development of PM of gastric cancer.This article is protected by copyright. All rights reserved.