Endometriosis occurs when endometrial-like tissue forms and grows outside the uterus due to oestrogen-induced epithelial-mesenchymal transition in the female reproductive tract. Factors that suppress this event could become potential therapeutic agents against disease occurrence and progression. However, an overview of these studies is still lacking. This review assessed the impact of a number factors on oestrogen-mediated epithelial-mesenchymal transition in the emergence of several diseases in the female reproductive tract, primarily endometriosis. The association between epithelial-mesenchymal transition and Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome was also investigated. Oestrogen, Wnt4 and epithelial-mesenchymal transition were chosen as keywords in Scopus, PubMed, and Web of Science searches performed on 28th June 2021. Study selection was refined to cancer-irrelevant, English, original articles published between years 2011–2021. The full-text assessment was carried out for topic-related articles after title and abstract screening. Included studies were summarised and assessed for their risk of bias using the Office of Health Assessment and Translation tool. In this review, 10 articles investigating oestrogen and epithelial-mesenchymal transition in the female reproductive tract were summarised and classified into two groups: seven studies under ‘factor’-modulated epithelial-mesenchymal transition and three studies under ‘factor’-manipulated oestrogen-induced epithelial-mesenchymal transition. The current evidence proposes that epithelial-mesenchymal transition is one of the prime causes of reproductive-related disease. This event could be mediated by distinct stimuli, specifically oestrogen and Wnt4 aberration. The results of this review suggest that oestrogen and Wnt4 participate in epithelial-mesenchymal transition in vaginal epithelial cells in MRKH syndrome, adopting from the theories of endometriosis development, which could therefore serve as a foundation for novel target treatment, specifically related to vaginal epithelialisation, to ensure better surgical outcomes.
Xeno-free three-dimensional cultures are gaining attention for mesenchymal stem cell (MSCs) expansion in clinical applications. We investigated the potential of xeno-free serum alternatives, human serum and human platelet lysate, to replace the current conventional use of foetal bovine serum for subsequent MSCs microcarrier cultures. In this study, Wharton’s Jelly MSCs were cultured in nine different media combinations to identify the best xeno-free culture media for MSCs culture. Cell proliferation and viability were identified, and the cultured MSCs were characterised in accordance with the minimal criteria for defining multipotent mesenchymal stromal cells by the International Society for Cellular Therapy (ISCT). The selected culture media was then used in the microcarrier culture of MSCs to determine the potential of a three-dimensional culture system in the expansion of MSCs for future clinical applications, and to identify the immunomodulatory potential of cultured MSCs. Low Glucose DMEM (LG) + Human Platelet (HPL) lysate media appeared to be good candidates for replacing conventional MSCs culture media in our monolayer culture system. MSCs cultured in LG-HPL achieved high cell yield, with characteristics that remained as described by ISCT, although the overall mitochondrial activity of the cells was lower than the control and the subsequent effects remained unknown. MSC microcarrier culture, on the other hand, showed comparable cell characteristics with monolayer culture, yet had stagnated cell proliferation, which is potentially due to the inactivation of FAK. Nonetheless, both the MSCs monolayer culture and the microcarrier culture showed high suppressive activity on TNF-α, and only the MSC microcarrier culture has a better suppression of IL-1 secretion. In conclusion, LG-HPL was identified as a good xeno-free media for WJMSCs culture, and although further mechanistic research is needed, the results show that the xeno-free three-dimensional culture maintained MSC characteristics and improved immunomodulatory activities, suggesting the potential of translating the monolayer culture into this culture system in MSC expansion for future clinical application.
Infertility is a condition affecting women who are born with an underdeveloped or absent vagina, a birth defect known as congenital absence of the vagina. It is a rare disorder where the development of the Mullerian duct is obstructed by unidentified causes. The case is seldom reported due to the low prevalence and sparse epidemiology studies worldwide. A potential solution for the disorder is neovaginal creation with in vitro cultured vaginal mucosa. Limited studies have reported its application, but none are reproducible or specific regarding the established processes for acquiring vaginal epithelial cells from vaginal biopsies. These research gaps were adequately answered with an epidemiology study of inpatient details in Hospital Canselor Tuanku Muhriz, Malaysia, established methods and outcomes of vaginal tissue processing and isolation, and characterization of vaginal epithelial cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and immunofluorescence assays. The reported evidence and speculation that the disorder arises because of a cellular transition event between epithelial and mesenchymal cells during the development of the Mullerian duct could be key in the creation of neovaginas using established culture procedures to improve surgical results and restore fertility.
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