Menstrual Blood-Derived Endometrial Stem Cells’ Impact for the Treatment Perspective of Female Infertility

Abstract

When looking for the causes and treatments of infertility, much attention is paid to one of the reproductive tissues—the endometrium. Therefore, endometrial stem cells are an attractive target for infertility studies in women of unexplained origin. Menstrual blood stem cells (MenSCs) are morphologically and functionally similar to cells derived directly from the endometrium; with dual expression of mesenchymal and embryonic cell markers, they proliferate and regenerate better than bone marrow mesenchymal stem cells. In addition, menstrual blood stem cells are extracted in a non-invasive and painless manner. In our study, we analyzed the characteristics and the potential for decidualization of menstrual blood stem cells isolated from healthy volunteers and women diagnosed with infertility. We demonstrated that MenSCs express CD44, CD166, CD16, CD15, BMSC, CD56, CD13 and HLA-ABC surface markers, have proliferative properties, and after induction of menstrual stem cell differentiation into epithelial direction, expression of genes related to decidualization (PRL, ESR, IGFBP and FOXO1) and angiogenesis (HIF1, VEGFR2 and VEGFR3) increased. Additionally, the p53, p21, H3K27me3 and HyperAcH4 proteins’ expression increased during MenSCs decidualization, they secrete proteins that are involved in the regulation of the actin cytoskeleton, estrogen and relaxin signaling pathways and the management of inflammatory processes. Our findings reveal the potential use of MenSCs for the treatment of reproductive disorders.

Mesenchymal Stem Cells-Induced Trophoblast Invasion Is Reduced in Patients with a Previous History of Preeclampsia

“…The extent of trophoblast invasion relies on communication between the placenta and maternal decidua. Studies have demonstrated increased decidualization markers such as IGFBP1 and prolactin in endometrial stromal cells after hormonal treatment [ 35 , 36 ]. Moreover, endometrial stromal cells of women with a history of PE failed to decidualize in vitro after hormonal treatment [ 9 ].…”

MicroRNA-146 attenuates lipopolysaccharide induced ovarian dysfunction by inhibiting the TLR4/NF- κB signaling pathway

“…Recent study reports that another therapeutic mechanism to prevent ovarian failure is to inhibit granulosa cells apoptosis, human placenta-derived mesenchymal stem cells (hPMSCs) can inhibit granulosa cells apoptosis by modulating stress levels controlled by the IRE1-a pathway [ 29 ]. One of the newest therapeutic approaches is to use stem cells extracted from human menstrual blood [ 30 ]. And the successful engraftment of mesenchymal stem cells was transplanted into the ovaries of cyclophosphamide (CTX)-induced POI model mice [ 31 ].…”

Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration

“…Chronic obstructive pulmonary disease is often associated with cigarette smoking exposure. Chen and co-workers studied the protective effects of adipose-derived stem cell-conditioned medium (ADSC-CM) against cigarette-smoke-extract-induced cell death and epithelial–mesenchymal transition (EMT) on human lung cancer and non-cancerous epithelial cells model [ 11 ]. ADSC-CM effectively inhibited EMT induced by cigarette smoke extract and was able to reverse the gradual loss of epithelial marker expression associated with TGF-β1 treatment.…”

“…Studies performed by Navakauskiene’s research group are focused on endometrial stem cells as an attractive target for studies on infertility of unexplained origin in women [ 11 ]. Menstrual-blood-origin stem cells are morphologically and functionally similar to cells derived from the endometrium.…”

“…They found that the induction of the menstrual stem cells for differentiation into epithelial cells increased expression of genes related to decidualization (PRL, ESR, IGFBP, and FOXO1) and angiogenesis (HIF1, VEGFR2, and VEGFR3). The authors suggest that stem cells of endometrial origin isolated from menstrual blood could be an alternative source of cellular therapy for the improvement of endometrium function for females with diagnosed unexplained infertility treatment [ 11 ].…”