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Research Paper|Volume 13, Issue 4|pp 5055—5068

MicroRNA-29a-3p delivery via exosomes derived from engineered human mesenchymal stem cells exerts tumour suppressive effects by inhibiting migration and vasculogenic mimicry in glioma

Zongpu Zhang1,2, Xing Guo1,2, Xiaofan Guo1,2, Rui Yu1,2,3, Mingyu Qian1,2, Shaobo Wang1,2, Xiao Gao1,2, Wei Qiu1,2, Qindong Guo1,2, Jianye Xu1,2, Zihang Chen1,2, Huizhi Wang1,2, Yanhua Qi1,2, Rongrong Zhao1,2, Hao Xue1,2, Gang Li1,2
  • 1Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan 250012, Shandong, China
  • 2Shandong Key Laboratory of Brain Function Remodeling, Jinan 250012, Shandong, China
  • 3Department of Neurosurgery, The Second Hospital of Shandong University, Jinan 250033, Shandong, China
* Equal contribution
Received: December 11, 2019Accepted: November 20, 2020Published: February 1, 2021
https://doi.org/10.18632/aging.202424

Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Vasculogenic mimicry (VM), the formation of an alternative microvascular circulation independent of VEGF-driven angiogenesis, is reluctant to anti-angiogenesis therapy for glioma patients. However, treatments targeting VM are lacking due to the poor understanding of the molecular mechanism involved in VM formation. By analysing the TCGA database, microRNA-29a-3p (miR-29a-3p) was found to be highly expressed in normal brain tissue compared with glioma. An in vitro study revealed an inhibitory role for miR-29a-3p in glioma cell migration and VM formation, and further study confirmed that ROBO1 is a direct target of miR-29a-3p. Based on this, we engineered human mesenchymal stem cells (MSCs) to produce miR-29a-3p-overexpressing exosomes. Treatment with these exosomes attenuated migration and VM formation in glioma cells. Moreover, the anti-glioma role of miR-29a-3p and miR-29a-3p-overexpressing exosomes were confirmed in vivo. Overall, the present study demonstrates that MSCs can be used to produce miR-29a-3p-overexpressing exosomes, which have great potential for anti-VM therapy and may act as supplements to anti-angiogenetic therapy in the clinic.