Investigating the role of menstrual blood stem cells in differentiating the expression of inflammatory and stem genes: indicators for the diagnosis and treatment of endometriosis
Investigating the role of menstrual blood stem cells in differentiating the expression of inflammatory and stem genes: indicators for the diagnosis and treatment of endometriosis
Mobina Rezaeijou,1Fatemeh Roozbahani,2,*
1. Islamic Azad University, Tehran Medical Branch 2. Department of Medical Microbiology and Virology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Introduction: From a scientific point of view, a stem cell is a non-specialized cell that has unlimited self-replication and the ability to differentiate into different types of cells. It is present in the menstrual environment. These cells have the stem cells of cord blood and brain and can cause damage. They are easily available and can be collected every month without the use of drugs or invasive procedures. They have potential for treating diseases such as prostate cancer, skin ulcers, infertility in old age, uterine adhesions, endometriosis, etc. Endometriosis is a condition in which endometrial glands and uterine stroma grow outside the uterine lining (endometrium) and uterine muscle. This tissue can occur in all tissues of the body except the spleen, but the most common location, occurring in 50% of cases, is the pelvis, particularly the ovaries. Menstruation in this environment can lead to the formation of chocolate cysts or endometriomas. The most common symptoms include regular monthly pain, infertility, and chronic pelvic pain. The cause of endometriosis is still unknown, but studies have shown that differences in the expression of certain genes in menstrual blood cells may contribute to the development of this disease. The purpose of this study is to investigate the differences in the expression of inflammatory genes ( IL-1β, COX-2,TNF-α), angiogenesis (VEGF), surface markers (CD10, CD9, ER-α (Estrogen Receptor)), stemness genes (OCT4, NANOG, and SOX2), and genes related to apoptosis (BAX and BCL-2) in the menstrual blood- derived mesenchymal stem cells of endometriosis patients (E-MenSCs) and healthy women, as well as to explore the use of NE-MenSCs (non-endometriosis derived mesenchymal stem cells) for early diagnosis and treatment of endometriosis.
Methods: Samples were taken from the menstrual blood of healthy and diseased women, and the menstrual blood of healthy women was also used to create a conditioned medium (CM) with stem cells (NE-MenSCs). Q-PCR and real-time flow cytometry experiments were used to investigate the differences in the expression levels of inflammatory genes, angiogenesis, surface markers, stemness genes and genes involved in apoptosis.
Results: The results obtained from real-time qPCR and flow cytometry tests showed that E-MenSCs have high cell proliferation, and the ratio of the BAX gene effective in apoptosis to the anti-apoptotic gene BCL-2 is lower compared to NE-MenSCs. In relation to surface marker genes, the expression level of CD9 was low compared to NE-MenSCS, while the expression level of ER-α and VEGF in E-MenSCs was higher than NE-MenSCs. Also, the expression level of CD10, which is an effective marker in the diagnosis of endometriosis, was higher in E-MenSCs, and significantly decreased after treatment with CM.. In addition, the inflammatory genes IL-1β and COX2, which had a higher expression in E-MenSCs, decreased in expression by 34.46% and 5.3%, respectively, after CM treatment. However, TNF-α, which had a low expression in E-MenSCs, had a significant increase in expression after CM treatment. The stemness genes OCT4 and NANOG, which had low expression in E-MenSCs, increased their expression by 52.8% and 18.53% respectively after treatment with CM, while SOX2 with high expression in E-MenSCs decreased by 64% after treatment with CM.
Conclusion: The investigation in this study showed that the use of conditioned medium (CM) derived from NE-MenSCs can have a positive effect on the expression of inflammatory genes, angiogenesi, stemness, and surface markers, as well as genes involved in apoptosis. However, further research and extensive testing are needed to fully understand the therapeutic potential of menstrual blood stem cells for the treatment of endometriosis.