Metformin as a potential agent for modulating the faulty endometriotic mesenchymal stem cells: A case-control study


Background: According to stem cell theory, it seems that the proliferation/differentiation imbalance in endometrial mesenchymal stem cells (enMSCs) is the leading cause of endometriosis, so targeting them to modulate stemness-relevant factors seems to be a wise choice for endometriosis treatment.

Objective: We aimed to investigate the effects of metformin on stemness properties of enMSCs by evaluating the expression profile of stemness-related genes and microRNAs (miRNAs).

Materials and Methods: In this case-control study, MSCs were isolated from the eutopic endometrium of 3 endometriotic and 3 healthy women. After their characterization and culture, they were treated with 0.1, 1, and 10 mM metformin for 72 hr. Finally, the expression of octamer-binding transcription factor (OCT) 4A, OCT4B, OCT4B1, sex determining region Y-Box transcription factor 2, nanog homeobox, microRNA-200b, microRNA-145, and lethal-7b were analyzed by quantitative reverse transcription-polymerase chain reaction.

Results: Metformin modulated the expression of stemness-related genes and miRNAs, OCT4A, OCT4B, OCT4B1, sex determining region Y-Box transcription factor 2, nanog homeobox, microRNA-200b, microRNA-145, and lethal-7b in enMSCs, especially at 1 and 10 mM concentration. Notably, metformin had a paradoxical effect on normal enMSCs.

Conclusion: We showed that metformin could modulate the expression of deregulated genes and miRNAs in faulty enMSCs, and restore their skewed selfrenewal/ differentiation balance. It might be a promising drug for endometriosis treatment. The paradoxical effect of metformin on enMSCs and normal enMSCs might be because of their different metabolic patterns. This drug requires further investigation to illustrate.

Key words: Endometriosis, Mesenchymal stem cells, Metformin.

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