# Exosomes from miR-149-3p-transfected menstrual blood-derived mesenchymal stem cells ameliorate inflammation and migration of endometriosis cells

## TL;DR

Exosomes carrying miR-149-3p from menstrual stem cells reduce inflammation and cell migration in endometriosis.

## Contribution

Exosomes from miR-149-3p-transfected MenSCs show therapeutic potential for endometriosis.

## Key findings

- Exosomes from miR-149-3p-transfected MenSCs reduced IL-6, IL-8, ROS, β-catenin, and Ki-67 levels.
- miR-149-3p transfection decreased IL-6 protein levels but not other inflammatory markers.
- Exosome treatment had broader anti-inflammatory effects than direct miRNA transfection.

## Abstract

Endometriosis carries remarkable social, public health, and financial consequences. Based on two theories of retrograde menstruation and stem cells, menstrual blood-derived stem cells (MenSCs) play a significant role in endometriosis since key genes of critical cellular processes are differentially expressed in the MenSCs of endometriosis and non-endometriosis women (E- and NE-MenSCs, respectively). In this study, E-MenSCs were isolated from the menstrual blood of women with various endometriosis subtypes. We tried to find the proper microRNA (miRNA) and assayed the effects of exosome-encapsulated miRNA on modulating the gene expression profile and functional pattern of E-MenSCs.

After in silico selection of miR-149-3p using publicly accessible algorithm-based databases, E- and NE-MenSCs were cultured as controls, and the other experimental groups were as follows: E-MenSCs transfected with empty and miRNA vectors (E-MenSC+BB and E-MenSC+miR), and E-MenSCs treated with exosomes derived from non-transfected and miRNA-transfected NE-MenSCs (E-MenSC+Exo and E-MenSC+T-Exo). Then, the expression level of selected genes, the level of interleukins (ILs) and oxygen reactive species (ROS), the protein level of β-catenin and Ki-67, and the migratory ability were assessed through real-time PCR, ELISA, western blot, and scratching tests, respectively.

Although both E-MenSCs+T-Exo and E-MenSC+miR showed down-regulation of IL-6, -8, and -10, neither had decreased IL-1β, vascular endothelial growth factor, IDO1, and KRAS levels. Furthermore, only the IL-6 protein level was significantly decreased in the E-MenSC+miR group, but the levels of IL-6, IL-8, ROS, β-catenin, and Ki67 were significantly lower in the E-MenSCs+T-Exo group compared to the E-MenSCs.

The potential of exosomes as miRNA carriers could be considered in developing novel endometriosis therapies.