Anti-inflammatory Effects of Mesenchymal Stem Cells-derived Exosomes on Endometriosis
Anti-inflammatory Effects of Mesenchymal Stem Cells-derived Exosomes on Endometriosis
Azar Sheikholeslami,1,*Faezeh Davoodi Asl,2Seyedeh Saeideh Sahraei,3Naser Kalhor,4Hoda Fazaeli,5Mohsen Sheykhhasan,6
1. Department of Mesenchymal Stem Cells, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran 3. Department of Reproductive Biology, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran 4. Department of Mesenchymal Stem Cells, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran 5. Department of Mesenchymal Stem Cells, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran 6. Department of Mesenchymal Stem Cells, Academic Center for Education, Culture, and Research (ACECR), Qom Branch, Qom, Iran
Introduction: Among the most prevalent disorders affecting women globally is endometriosis. Endometriosis has become more common recently as a result of a number of genetic and environmental causes. Inflammation is one of the key pathogenic processes associated with endometriosis. We used exosomes formed from menstrual blood-derived stem cells (MenSCs) to treat endometriotic stem cells since the therapeutic effects of mesenchymal stem cells are delivered through paracrine functions and generation of extracellular vesicles and exosomes containing various growth factors and cytokines.
Methods: Menstrual blood samples (2-3 ml) from healthy and endometriosis women were collected. MenSCs were isolated by the Ficoll density-gradient centrifugation and characterized by flow cytometry. Secreted exosomes were isolated from healthy MenSCs (NE-MenSCs) based on the protocol of the Exocib kit (Cib Biotech Co) and used to treat endometriotic cells (E-MenSCs).
various genes related inflammation, were analyzed using Real-Time PCR, from which some were evaluated in protein level as well.
Results: We evaluated several key inflammatory genes that are expressed at high or moderate levels in MenSCs. Compared with NE-MenSCs, E-MenSCs showed higher expression of IL-1β, IL-6 and IL-8. NF-kB, and COX-2, while similar expression of HIF and TNF-α genes was observed in both healthy and endometriosis cell lines.
MSC-Exo surprisingly suppressed all inflammatory genes studied in the endometriosis cell line compared to untreated E-MenSCs.
two main inflammatory markers IL-6 and IL-8 were analyzed using ELISA method.
IL-6 and IL-8 were expressed at a lower level in E-MenSCs treated with MSC-Exo than in untreated E-MenSCs.
ER expression may serve as a prognostic biomarker of aggressive endometriosis.
ER-α gene had remarkably higher expression in E-MenSCs rather than NE-MenSCs.
It was observed that MSC-Exo did not change ER-a gene expression levels in the E-MenSCs group as compared to NE-MenSCs.
ELISA was performed to quantify the ER-a concentration. ER-α expression showed no significant change after exosome-treated E-MenSCs.
Conclusion: MenSCs-derived exosomes can be used as a better therapeutic option for the improvement of endometriosis compared to conventional treatments.
The present study shows that exosomes isolated from menstrual blood stem cells reduce the abnormal secretion of inflammatory factors as well as cell proliferation in endometriosis cells.