Current advances in understanding endometrial epithelial cell biology and therapeutic applications for intrauterine adhesion

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Abstract

The human endometrium is a highly regenerative tissue capable of undergoing scarless repair during the menstruation and postpartum phases. This process is mediated by endometrial adult stem/progenitor cells. During the healing of endometrial injuries, swift reepithelization results in the rapid covering of the wound surface and facilitates subsequent endometrial restoration. The involvement of endogenous endometrial epithelial stem cells, stromal cells, and bone marrow-derived cells in the regeneration of the endometrial epithelium has been a subject of prolonged debate. Increasing evidence suggests that the regeneration of the endometrial epithelium mainly relies on epithelial stem cells rather than stromal cells and bone marrow-derived cells. Currently, no consensus has been established on the identity of epithelial stem cells in the epithelial compartment. Several markers, including stage-specific embryonic antigen-1 (SSEA-1), sex-determining region Y-box 9 (SOX9), neural-cadherin (N-cadherin), leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5), CD44, axis inhibition protein 2 (Axin2), and aldehyde dehydrogenase 1A1 (ALDH1A1), have been suggested as potential candidate markers for endometrial epithelial stem cells. The identification of endometrial epithelial stem cells contributes to our understanding of endometrial regeneration and offers new therapeutic insights into diseases characterized by regenerative defects in the endometrium, such as intrauterine adhesion. This review explores different perspectives on the origins of human and mouse endometrial epithelial cells. It summarizes the potential markers, locations, and hierarchies of epithelial stem cells in both human and mouse endometrium. It also discusses epithelial cell-based treatments for intrauterine adhesion, hoping to inspire further research and clinical application of endometrial epithelial stem cells.

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Most cited references 144

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Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities.

Roel Nusse, Hans Clevers (2017)

The WNT signal transduction cascade is a main regulator of development throughout the animal kingdom. Wnts are also key drivers of most types of tissue stem cells in adult mammals. Unsurprisingly, mutated Wnt pathway components are causative to multiple growth-related pathologies and to cancer. Here, we describe the core Wnt/β-catenin signaling pathway, how it controls stem cells, and contributes to disease. Finally, we discuss strategies for Wnt-based therapies.

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Record: found
Abstract: found
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In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration.

Meritxell Huch, Craig Dorrell, Sylvia F Boj … (2013)

The Wnt target gene Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5) marks actively dividing stem cells in Wnt-driven, self-renewing tissues such as small intestine and colon, stomach and hair follicles. A three-dimensional culture system allows long-term clonal expansion of single Lgr5(+) stem cells into transplantable organoids (budding cysts) that retain many characteristics of the original epithelial architecture. A crucial component of the culture medium is the Wnt agonist RSPO1, the recently discovered ligand of LGR5. Here we show that Lgr5-lacZ is not expressed in healthy adult liver, however, small Lgr5-LacZ(+) cells appear near bile ducts upon damage, coinciding with robust activation of Wnt signalling. As shown by mouse lineage tracing using a new Lgr5-IRES-creERT2 knock-in allele, damage-induced Lgr5(+) cells generate hepatocytes and bile ducts in vivo. Single Lgr5(+) cells from damaged mouse liver can be clonally expanded as organoids in Rspo1-based culture medium over several months. Such clonal organoids can be induced to differentiate in vitro and to generate functional hepatocytes upon transplantation into Fah(-/-) mice. These findings indicate that previous observations concerning Lgr5(+) stem cells in actively self-renewing tissues can also be extended to damage-induced stem cells in a tissue with a low rate of spontaneous proliferation.

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Synthetic alternatives to Matrigel

Elizabeth A Aisenbrey, William L. Murphy (2020)

Matrigel, a basement-membrane matrix extracted from Engelbreth–Holm–Swarm mouse sarcomas, has been used for more than four decades for a myriad of cell culture applications. However, Matrigel is limited in its applicability to cellular biology, therapeutic cell manufacturing and drug discovery owing to its complex, ill-defined and variable composition. Variations in the mechanical and biochemical properties within a single batch of Matrigel — and between batches — have led to uncertainty in cell culture experiments and a lack of reproducibility. Moreover, Matrigel is not conducive to physical or biochemical manipulation, making it difficult to fine-tune the matrix to promote intended cell behaviours and achieve specific biological outcomes. Recent advances in synthetic scaffolds have led to the development of xenogenic-free, chemically defined, highly tunable and reproducible alternatives. In this Review, we assess the applications of Matrigel in cell culture, regenerative medicine and organoid assembly, detailing the limitations of Matrigel and highlighting synthetic scaffold alternatives that have shown equivalent or superior results. Additionally, we discuss the hurdles that are limiting a full transition from Matrigel to synthetic scaffolds and provide a brief perspective on the future directions of synthetic scaffolds for cell culture applications. Matrigel is widely used for cell culture; however, its ill-defined composition, batch-to-batch variability, and animal-derived nature lead to experimental uncertainty and a lack of reproducibility. In this Review, we discuss the limitations of Matrigel and highlight synthetic alternatives for stem cell culture, regenerative medicine and organoid assembly.

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Author and article information

Contributors

Ruijin Wu:

ORCID: http://orcid.org/0000-0002-0144-7707

wurj@zju.edu.cn

Journal

Journal ID (nlm-ta): Stem Cell Res Ther

Journal ID (iso-abbrev): Stem Cell Res Ther

Title: Stem Cell Research & Therapy

Publisher: BioMed Central (London )

ISSN (Electronic): 1757-6512

Publication date (Electronic): 25 October 2024

Publication date PMC-release: 25 October 2024

Publication date Collection: 2024

Volume: 15

Electronic Location Identifier: 379

Affiliations

[1 ]GRID grid.13402.34, ISNI 0000 0004 1759 700X, Women’s Hospital, Zhejiang University School of Medicine, ; No. 1 Xueshi Road, Hangzhou, 310006 Zhejiang People’s Republic of China

[2 ]Zhejiang Key Laboratory of Maternal and Infant Health, Hangzhou, People’s Republic of China

[3 ]Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, People’s Republic of China

Author information

Ruijin Wu http://orcid.org/0000-0002-0144-7707

Article

Publisher ID: 3989

DOI: 10.1186/s13287-024-03989-6

PMC ID: 11515228

PubMed ID: 39456113

SO-VID: 00d4d195-6f25-4167-9bc7-f6cef8fbf0e3

License:

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

History

Date received : 25 April 2024

Date accepted : 9 October 2024

Funding

Funded by: “4 + X” Clinical Research Project of Women Hospital, Zhejiang University

Award ID: ZDFY2022-4XB102

Award Recipient : Ruijin Wu

Funded by: Zhejiang Medical Health Science and Technology Plan

Award ID: WKJ-ZJ-2321

Award Recipient : Ruijin Wu

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 82001519

Award Recipient : Hong Zhan

Funded by: Provincial Natural Science Foundation of Zhejiang

Award ID: LQ20H040006

Award Recipient : Hong Zhan

Custom metadata

ScienceOpen disciplines: Molecular medicine

Keywords: endometrial epithelial cells,epithelial stem cells,intrauterine adhesion,endometrial regeneration

Data availability:

ScienceOpen disciplines: Molecular medicine

Keywords: endometrial epithelial cells, epithelial stem cells, intrauterine adhesion, endometrial regeneration

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