Exosomes derived from microRNA-584 transfected mesenchymal stem cells: novel alternative therapeutic vehicles for cancer therapy

Abstract

Exosomes are small membranous vesicles which contain abundant RNA molecules, and are transferred from releasing cells to uptaking cells. MicroRNA (miRNA) is one of the transferred molecules affecting the adopted cells, including glioma cells. We hypothesized that mesenchymal stem cells (MSCs) can secrete exosomes loading miRNA and have important effects on the progress of gliomas. To determine these effects by treating exosomal miRNA in culture media of miRNA mimic transfected MSCs, we assessed the in vitro cell proliferation and invasion capabilities, and the expression level of relative proteins associated with cell apoptosis, growth and migration. For animal studies, the mice injected with U87 cells were exposed to exosomes derived from miRNA-584-5p transfected MSCs, to confirm the influence of exosomal miRNA on the progress of glioma. Based on our results, we propose a new targeted cancer therapy wherein exosomes derived from miRNA transfected MSCs could be used to modulate tumor progress as the anticancer vehicles.

Exosomal microRNAs derived from mesenchymal stem cells: cell-to-cell messages

“…Studies confirmed that of the MSCs engrafted at these sites of injury most MSCs are largely cleared, and only some of them do get through to the injured target tissue [91]. The tropism of MSCs is based on their inherent homing ability towards injury sites in response to factors and substances that are released from injured tissue [92]. In these tissues, MSCs release pro-angiogenic factors and EVs which contain functional molecules such as miRNAs.…”

“…Another study reported inhibition of in vitro angiogenesis via exosomal transfer of miR-100 with decreased levels of vascular endothelial growth factor [131]. Overexpression of miR-146b and miR-584-5p in transfected MSCs resulted in down-regulation of anti-apoptotic genes, up-regulation of pro-apoptotic genes and suppression of tumor growth in an in vivo malignant glioma model [92,132].…”

Exosomal noncoding RNAs in Glioma: biological functions and potential clinical applications

“…Tumor-derived exosomes can change the behavior of surrounding stromal cells, which ultimately create a suitable microenvironment for tumor growth [24]. Meanwhile, stromal cells in the tumor microenvironment can in turn affect tumor progression through the release of exosomes [25][26][27][28][29][30]. Thus, the complex Fig.…”

Role of exosomes in malignant glioma: microRNAs and proteins in pathogenesis and diagnosis

“…miR-584 affects the expression of CYP2J2, which is related to the development of metastasis. A study by Kim et al specifically analyzed the role of miR-584 in the progression of glioma [113]. They studied this phenomenon by adding miRNA-containing exosomes to the media of cultured MSCs, which had been transfected by a miRNA mimic.…”