A Comparative Study of Gene Expression in Menstrual Blood-Derived Stromal Cells between Endometriosis and Healthy Women

Abstract

Background. Research into the pathogenesis of endometriosis would substantially promote its effective treatment and early diagnosis. Currently, accumulating evidence has shed light on the importance of endometrial stem cells within the menstrual blood which are involved in the establishment and progression of endometriotic lesions in a retrograde manner. Objectives. We aimed to identify the differences in some genes’ expression between menstrual blood-derived mesenchymal stem cells (MenSCs) isolated from endometriosis patients (E-MenSCs) and MenSCs from healthy women (NE-MenSCs). Methods. Menstrual blood samples (2-3 mL) from healthy and endometriosis women in the age range of 22–35 years were collected. Isolated MenSCs by the Ficoll-Paque density-gradient centrifugation method were characterized by flow cytometry. MenSCs were evaluated for key related endometriosis genes by real-time-PCR. Results. E-MenSCs were morphologically different from NE-MenSCs and showed, respectively, higher and lower expression of CD10 and CD9. Furthermore, E-MenSCs had higher expression of Cyclin D1 (a cell cycle-related gene) and MMP-2 and MMP-9 (migration- and invasion-related genes) genes compared with NE-MenSCs. Despite higher cell proliferation in E-MenSCs, the BAX/BCL-2 ratio was significantly lower in E-MenSCs compared to NE-MenSCs. Also, the level of inflammatory genes such as IL1β, IL6, IL8, and NF-κB and stemness genes including SOX2 and SALL4 was increased in E-MenSCs compared with NE-MenSCs. Further, VEGF, as a potent angiogenic factor, showed a significant increase in E-MenSCs rather than NE-MenSCs. However, NE-MenSCs showed increased ER-α and β-catenin when compared with E-MenSCs. Conclusion. Here, we showed that there are gene expression differences between E-MenSCs and NE-MenSCs. These findings propose that MenSCs could play key role in the pathogenesis of endometriosis and further support the menstrual blood retrograde theory of endometriosis formation. This could be of great importance in exploiting promising therapeutic targets and new biomarkers for endometriosis treatment and prognosis.

Interferon Signaling in the Endometrium and in Endometriosis

“…The expression of inflammatory genes, such as IL-1β , IL-6 , IL-8 , and NF-κB , and that of stemness genes, including SRY-Box Transcription Factor 2 ( SOX2 ) and Spalt Like Transcription Factor 4 ( SALL4 ), is also highly elevated in endometriotic MSCs compared with normal MSCs. Furthermore, endometriotic MSCs express higher levels of VEGF than normal MSCs [ 92 ]. Ectopic MSCs exhibit more aggressive migration and invasion characteristics than eutopic MSCs in vivo and in vitro [ 91 ].…”

What Do the Transcriptome and Proteome of Menstrual Blood-Derived Mesenchymal Stem Cells Tell Us about Endometriosis?

“…Consequently, they are considered a promising tool for regenerative medicine [ 1 , 2 , 3 ]. Due to the varied potential of clinical applications combined with no ethical dilemma, MenSCs have gained prominence in the scientific community since their discovery in 2007 [ 4 ] in different gynecological diseases [ 5 ] and, therefore, in the context of endometriosis [ 6 , 7 , 8 , 9 ]. Particular emphasis has been given to the different functionalities of these progenitor cells regarding the etiopathogenic mechanism [ 8 ] and reproductive aspects of endometriosis [ 10 ].…”

Novel in vivo endometriotic models associated eutopic endometrium by implanting menstrual blood-derived stromal cells from patients with endometriosis

“…In addition, a new contemporary study 28 indicates that E-MenSCs had higher expression of Cyclin D1 (a cell cycle-related gene), MMP2 and MMP9 (migration- and invasion-related genes), and SOX2 and SALL4 (stemness genes) genes compared with H-MenSCs. In our research, we demonstrated that implanting cell density truly played a role in cell proliferation ability: the proliferation ability of H-MenSCs (1 × 10 5 cells/mL) surpassed E-MenSCs with lower density (5 × 10 4 cells/mL), while E-MenSCs are still superior to H-MenSCs at the same lower density (5 × 10 4 cells/mL).…”