Comparison of Organoids from Menstrual Fluid and Hormone-Treated Endometrium: Novel Tools for Gynecological Research

Filby, Caitlin E.; Wyatt, Katherine A.; Mortlock, Sally; Cousins, Fiona L.; McKinnon, Brett; Tyson, Kate E.; Montgomery, Grant W.; Gargett, Caroline E.

doi:10.3390/jpm11121314

Cited by 17 publications

(15 citation statements)

References 31 publications

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“…The role of epigenetics in the development of endometriosis has been investigated using organoids derived from ectopic and eutopic endometrium from endometriosis patients 154 . Recently, menstrual fluid organoids have been established which reflect the same properties as those derived from endometrial tissue 155,156 . The efficiency and non‐invasive method for obtaining endometrial cells from menstrual fluid presents a promising avenue for personalized medicine and tailoring drug treatments for individual endometriosis patients.…”

Section: Influence Of New Technologies On Understanding Endometriosis...mentioning

confidence: 99%

“… 154 Recently, menstrual fluid organoids have been established which reflect the same properties as those derived from endometrial tissue. 155 , 156 The efficiency and non‐invasive method for obtaining endometrial cells from menstrual fluid presents a promising avenue for personalized medicine and tailoring drug treatments for individual endometriosis patients.…”

Section: Influence Of New Technologies On Understanding Endometriosis...mentioning

confidence: 99%

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New concepts on the etiology of endometriosis

Cousins

McKinnon

Mortlock

et al. 2023

J of Obstet and Gynaecol

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Endometriosis is a serious, chronic disorder where endometrial tissue grows outside the uterus, causing severe pelvic pain and infertility. It affects 11% of women. Endometriosis is a multifactorial disorder of unclear etiology, although retrograde menstruation plays a major role. It has a genetic component with over 40 genetic risk factors mapped, although their mechanism of action is still emerging. New evidence suggests a role for retrograde menstruation of endometrial stem/progenitor cells, now that identifying markers of these cells are available. Recent lineage tracing and tissue clearing microscopy and 3D reconstruction has provided new understanding of endometrial glandular structure, particularly the horizontal orientation and interconnection of basalis glands. New sequencing technologies, particularly whole genome DNA sequencing are revealing somatic mutations, including in cancer driver genes, in normal and eutopic endometrium of patients with endometriosis, as well as ectopic endometriotic lesions. Methylome sequencing is offering insight into the regulation of genes and the role of the environmental factors. Single cell RNA sequencing reveals the transcriptome of individual endometrial cells, shedding new light on the diversity and range of cellular subpopulations of the major cell types present in the endometrium and in endometriotic lesions. New endometrial epithelial organoid cultures replicating glandular epithelium are providing tractable models for studying endometriosis. Organoids derived from menstrual fluid offer a non‐invasive source of endometrial tissue and a new avenue for testing drugs and developing personalized medicine for treating endometriosis. These new approaches are rapidly advancing our understanding of endometriosis etiology.

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Section: Influence Of New Technologies On Understanding Endometriosis...mentioning

confidence: 99%

Section: Influence Of New Technologies On Understanding Endometriosis...mentioning

confidence: 99%

New concepts on the etiology of endometriosis

Cousins

McKinnon

Mortlock

et al. 2023

J of Obstet and Gynaecol

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“…Organoids can be generated from shed endometrial tissue in menstrual fluid (MFO) ( 89 , 90 ) ( Figure 2 , red box).While MFO are less abundant than EMO, they appear to represent EMO in proliferation rates, responses to hormones, and gene expression profiles ( 89 , 90 ). They can also be derived from disease states including endometriosis and adenomyosis.…”

Section: Stem/progenitors In In Vitro Models Of Me...mentioning

confidence: 99%

Endometrial Stem/Progenitor Cells–Their Role in Endometrial Repair and Regeneration

Cousins

Filby

Gargett

2022

Front. Reprod. Health

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The human endometrium is a remarkable tissue, undergoing ~450 cycles of proliferation, differentiation, shedding (menstruation), repair, and regeneration over a woman's reproductive lifespan. Post-menstrual repair is an extremely rapid and scar-free process, with re-epithelialization of the luminal epithelium completed within 48 h of initiation of shedding. Following menstruation, the functionalis grows from the residual basalis layer during the proliferative phase under the influence of rising circulating estrogen levels. The regenerative capacity of the endometrium is attributed to stem/progenitor cells which reside in both the epithelial and stromal cell compartments of the basalis layer. Finding a definitive marker for endometrial epithelial progenitors (eEPCs) has proven difficult. A number of different markers have been suggested as putative progenitor markers including, N-cadherin, SSEA-1, AXIN2, SOX-9 and ALDH1A1, some of which show functional stem cell activity in in vitro assays. Each marker has a unique location(s) in the glandular epithelium, which has led to the suggestion that a differentiation hierarchy exists, from the base of epithelial glands in the basalis to the luminal epithelium lining the functionalis, where epithelial cells express different combinations of markers as they differentiate and move up the gland into the functionalis away from the basalis niche. Perivascular endometrial mesenchymal stem cells (eMSCs) can be identified by co-expression of PDGFRβ and CD146 or by a single marker, SUSD2. This review will detail the known endometrial stem/progenitor markers; their identity, location and known interactions and hierarchy across the menstrual cycle, in particular post-menstrual repair and estrogen-driven regeneration, as well as their possible contributions to menstruation-related disorders such as endometriosis and regeneration-related disorder Asherman's syndrome. We will also highlight new techniques that allow for a greater understanding of stem/progenitor cells' role in repair and regeneration, including 3D organoids, 3D slice cultures and gene sequencing at the single cell level. Since mouse models are commonly used to study menstruation, repair and regeneration we will also detail the mouse stem/progenitor markers that have been investigated in vivo.

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“…Generally, endometrial epithelial and stromal cells can be isolated from an endometrial biopsy, however, this is collected in a clinical setting by an invasive transcervical procedure. Our goal was to develop a non-invasive method for the isolation of paired endometrial epithelial organoids and stromal cells from menstrual fluid collected in a reusable menstrual cup ( 9 ) from individual women, based on recent reports describing the isolation of endometrial epithelial organoids or endometrial stromal cells from menstrual fluid ( 10 – 12 ).…”

Section: Introductionmentioning

confidence: 99%

From cup to dish: how to make and use endometrial organoid and stromal cultures derived from menstrual fluid

Hewitt,

Dickson,

Edwards

et al. 2023

Front. Endocrinol.

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Diseases impacting the female reproductive tract pose a critical health concern. The establishment of in vitro models to study primary endometrial cells is crucial to understanding the mechanisms that contribute to normal endometrial function and the origins of diseases. Established protocols for endometrial stromal cell culture have been in use for decades but recent advances in endometrial organoid culture have paved the way to allowing study of the roles of both epithelial and stromal endometrial cells in vitro. Due to inter-individual variability, primary cell cultures must be established from numerous persons. Generally, endometrial epithelial and stromal cells can be isolated from an endometrial biopsy, however, this is collected in a clinical setting by an invasive transcervical procedure. Our goal was to develop a non-invasive method for the isolation of paired endometrial epithelial organoids and stromal cells from menstrual fluid collected from individual women, based on recent reports describing the isolation of endometrial epithelial organoids or endometrial stromal cells from menstrual fluid. Participants recruited by the NIEHS Clinical Research Unit were provided with a menstrual cup and instructed to collect on the heaviest day of their menstrual period. Endometrial tissue fragments in the menstrual fluid samples were washed to remove blood, minced, and digested with proteinases. Following digestion, the solution was strained to separate epithelial fragments from stromal cells. Epithelial fragments were washed, resuspended in Matrigel, and plated for organoid formation. Stromal cells were separated from residual red blood cells using a Ficoll gradient and then plated in a flask. Once established, estrogen responsiveness of endometrial epithelial organoids was assessed and the decidual response of stromal cells was evaluated. Following treatments, qPCR was performed on organoids for genes induced by estradiol and on stromal cells for genes induced by decidualization. In this manner, the relative responsiveness of paired organoid and stroma cell cultures isolated from each woman could be assessed. In conclusion, we can isolate both epithelial and stromal cells from a single menstrual fluid sample, allowing us to establish organoids and cells in a paired manner. This protocol can greatly enhance our knowledge of the role of epithelial and stromal cells alone and in coordination.

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Comparison of Organoids from Menstrual Fluid and Hormone-Treated Endometrium: Novel Tools for Gynecological Research

Cited by 17 publications

References 31 publications

New concepts on the etiology of endometriosis

New concepts on the etiology of endometriosis

Endometrial Stem/Progenitor Cells–Their Role in Endometrial Repair and Regeneration

From cup to dish: how to make and use endometrial organoid and stromal cultures derived from menstrual fluid

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