Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Clinical Medicine, Cell, and Organism Physiology".

Deadline for manuscript submissions: closed (20 September 2021) | Viewed by 55523

Special Issue Editors


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Guest Editor
Hudson Institute of Medical Research, The Ritchie Centre, Clayton, Australia
Interests: endometrial epithelial progenitor cells; endometrial mesenchymal stem cells; endometriosis, pelvic organ prolapse; tissue engineering

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Guest Editor
Department of Women’s and Children’s Health, Institute of Translational Medicine, University of Liverpool, Liverpool Women’s Hospital, Crown Street, Liverpool L8 7SS, UK
Interests: endometrial regeneration; epithelial stem cells; endometriosis; endometrial cancer

Special Issue Information

Dear Colleagues,

The human endometrium is one of the most regenerative tissues in the body, undergoing unique cycles of menstrual shedding and regeneration over 400 times during reproductive life. Each month, approximately one centimetre of mucosal tissue, comprising glands and stroma, is generated. This phenomenon is not shared by any typical model organisms which undergo sexual reproduction and is likely mediated by endometrial stem/progenitor cells. Several types of stem/progenitor cells have been identified: endometrial mesenchymal stem cells, endometrial epithelial progenitor cells and side population cells comprising a heterogeneous population, predominantly endothelial cells.

This Special Issue aims to highlight the challenges in endometrial stem/progenitor cell research, the importance of characterising these rare populations and the issues to consider in developing them for stem cell therapies. The application of endometrial stem/progenitor cells as a cell-based therapy for treating disorders will be welcomed.

Areas to be covered in this Special Issue may include but are not limited to: recent evidence of cell-based therapies utilising endometrial derived mesenchymal stem cells, endometrial epithelial progenitors, topics including endometrial clonal evolution, mutation burden, 3D histoarchitecture and endometrial epithelial organoids and next generation sequencing at the single cell level, which may have important relevance to endometrial stem/ progenitor cell biology and application in personalised medicine.

We expect that this Special Issue will provide novel information on the abovementioned topics and will be of interest to scientists and clinicians already working or seeking to undertake research at the intersection of endometrial stem cell biology and cell-based therapies. Therefore, contributions by experts in the field, in the form of original research papers and reviews are most welcome.

Prof. Caroline E. Gargett
Prof. Dharani Hapangama
Guest Editors

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Keywords

  • Endometrial stem/progenitor cells 
  • Mesenchymal stem cells 
  • Epithelial progenitor cells 
  • Endometrial regeneration 
  • Stem/progenitor cell therapy 
  • Ovarian steroid hormones 
  • Endometriosis 
  • Endometrial cancer 
  • Tissue engineering 
  • Cell-based therapies

Published Papers (14 papers)

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Editorial

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5 pages, 201 KiB  
Editorial
Endometrial Stem/Progenitor Cells: Prospects and Challenges
by Caroline E. Gargett and Dharani Hapangama
J. Pers. Med. 2022, 12(9), 1466; https://doi.org/10.3390/jpm12091466 - 07 Sep 2022
Cited by 1 | Viewed by 1450
Abstract
The human endometrium is one of the most regenerative tissues in the body, undergoing over 400 cycles of menstrual shedding and regeneration during reproductive life [...] Full article
(This article belongs to the Special Issue Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges)

Research

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14 pages, 4049 KiB  
Communication
Comparison of Organoids from Menstrual Fluid and Hormone-Treated Endometrium: Novel Tools for Gynecological Research
by Caitlin E. Filby, Katherine A. Wyatt, Sally Mortlock, Fiona L. Cousins, Brett McKinnon, Kate E. Tyson, Grant W. Montgomery and Caroline E. Gargett
J. Pers. Med. 2021, 11(12), 1314; https://doi.org/10.3390/jpm11121314 - 06 Dec 2021
Cited by 10 | Viewed by 3511
Abstract
Endometrial organoids (EMO) are an important tool for gynecological research but have been limited by generation from (1) invasively acquired tissues and thus advanced disease states and (2) from women who are not taking hormones, thus excluding 50% of the female reproductive-aged population. [...] Read more.
Endometrial organoids (EMO) are an important tool for gynecological research but have been limited by generation from (1) invasively acquired tissues and thus advanced disease states and (2) from women who are not taking hormones, thus excluding 50% of the female reproductive-aged population. We sought to overcome these limitations by generating organoids from (1) menstrual fluid (MF; MFO) using a method that enables the concurrent isolation of menstrual fluid supernatant, stromal cells, and leukocytes and (2) from biopsies and hysterectomy samples from women taking hormonal medication (EMO-H). MF was collected in a menstrual cup for 4–6 h on day 2 of menstruation. Biopsies and hysterectomies were obtained during laparoscopic surgery. Organoids were generated from all sample types, with MFO and EMO-H showing similar cell proliferation rates, proportion and localization of the endometrial basalis epithelial marker, Stage Specific Embryonic Antigen-1 (SSEA-1), and gene expression profiles. Organoids from different disease states showed the moderate clustering of epithelial secretory and androgen receptor signaling genes. Thus, MFO and EMO-H are novel organoids that share similar features to EMO but with the advantage of (1) MFO being obtained non-invasively and (2) EMO-H being obtained from 50% of the women who are not currently being studied through standard methods. Thus, MFO and EMO-H are likely to prove to be invaluable tools for gynecological research, enabling the population-wide assessment of endometrial health and personalized medicine. Full article
(This article belongs to the Special Issue Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges)
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16 pages, 4317 KiB  
Article
Improved Models of Human Endometrial Organoids Based on Hydrogels from Decellularized Endometrium
by Emilio Francés-Herrero, Elena Juárez-Barber, Hannes Campo, Sara López-Martínez, Lucía de Miguel-Gómez, Amparo Faus, Antonio Pellicer, Hortensia Ferrero and Irene Cervelló
J. Pers. Med. 2021, 11(6), 504; https://doi.org/10.3390/jpm11060504 - 03 Jun 2021
Cited by 21 | Viewed by 4627
Abstract
Organoids are three-dimensional (3D) multicellular tissue models that mimic their corresponding in vivo tissue. Successful efforts have derived organoids from primary tissues such as intestine, liver, and pancreas. For human uterine endometrium, the recent generation of 3D structures from primary endometrial cells is [...] Read more.
Organoids are three-dimensional (3D) multicellular tissue models that mimic their corresponding in vivo tissue. Successful efforts have derived organoids from primary tissues such as intestine, liver, and pancreas. For human uterine endometrium, the recent generation of 3D structures from primary endometrial cells is inspiring new studies of this important tissue using precise preclinical models. To improve on these 3D models, we decellularized pig endometrium containing tissue-specific extracellular matrix and generated a hydrogel (EndoECM). Next, we derived three lines of human endometrial organoids and cultured them in optimal and suboptimal culture expansion media with or without EndoECM (0.01 mg/mL) as a soluble additive. We characterized the resultant organoids to verify their epithelial origin, long-term chromosomal stability, and stemness properties. Lastly, we determined their proliferation potential under different culture conditions using proliferation rates and immunohistochemical methods. Our results demonstrate the importance of a bioactive environment for the maintenance and proliferation of human endometrial organoids. Full article
(This article belongs to the Special Issue Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges)
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14 pages, 2392 KiB  
Article
Generation of Therapeutically Potent Spheroids from Human Endometrial Mesenchymal Stem/Stromal Cells
by Alisa Domnina, Larisa Alekseenko, Irina Kozhukharova, Olga Lyublinskaya, Mariia Shorokhova, Valeriy Zenin, Irina Fridlyanskaya and Nikolay Nikolsky
J. Pers. Med. 2021, 11(6), 466; https://doi.org/10.3390/jpm11060466 - 25 May 2021
Cited by 4 | Viewed by 2045
Abstract
Endometrial mesenchymal stem/stromal cells (eMSCs) hold great promise in bioengineering and regenerative medicine due to their high expansion potential, unique immunosuppressive properties and multilineage differentiation capacity. Usually, eMSCs are maintained and applied as a monolayer culture. Recently, using animal models with endometrial and [...] Read more.
Endometrial mesenchymal stem/stromal cells (eMSCs) hold great promise in bioengineering and regenerative medicine due to their high expansion potential, unique immunosuppressive properties and multilineage differentiation capacity. Usually, eMSCs are maintained and applied as a monolayer culture. Recently, using animal models with endometrial and skin defects, we showed that formation of multicellular aggregates known as spheroids from eMSCs enhances their tissue repair capabilities. In this work, we refined a method of spheroid formation, which makes it possible to obtain well-formed aggregates with a narrow size distribution both at early eMSC passages and after prolonged cultivation. The use of serum-free media allows this method to be used for the production of spheroids for clinical purposes. Wound healing experiments on animals confirmed the high therapeutic potency of the produced eMSC spheroids in comparison to the monolayer eMSC culture. Full article
(This article belongs to the Special Issue Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges)
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17 pages, 5919 KiB  
Article
Stromal Heterogeneity in the Human Proliferative Endometrium—A Single-Cell RNA Sequencing Study
by Suzanna Queckbörner, Carolina von Grothusen, Nageswara Rao Boggavarapu, Roy Mathew Francis, Lindsay C. Davies and Kristina Gemzell-Danielsson
J. Pers. Med. 2021, 11(6), 448; https://doi.org/10.3390/jpm11060448 - 22 May 2021
Cited by 26 | Viewed by 3849
Abstract
The endometrium undergoes regular regeneration and stromal proliferation as part of the normal menstrual cycle. To better understand cellular interactions driving the mechanisms in endometrial regeneration we employed single-cell RNA sequencing. Endometrial biopsies were obtained during the proliferative phase of the menstrual cycle [...] Read more.
The endometrium undergoes regular regeneration and stromal proliferation as part of the normal menstrual cycle. To better understand cellular interactions driving the mechanisms in endometrial regeneration we employed single-cell RNA sequencing. Endometrial biopsies were obtained during the proliferative phase of the menstrual cycle from healthy fertile women and processed to single-cell suspensions which were submitted for sequencing. In addition to known endometrial cell types, bioinformatic analysis revealed multiple stromal populations suggestive of specific stromal niches with the ability to control inflammation and extracellular matrix composition. Ten different stromal cells and two pericyte subsets were identified. Applying different R packages (Seurat, SingleR, Velocyto) we established cell cluster diversity and cell lineage/trajectory, while using external data to validate our findings. By understanding healthy regeneration in the described stromal compartments, we aim to identify points of further investigation and possible targets for novel therapy development for benign gynecological disorders affecting endometrial regeneration and proliferation such as endometriosis and Asherman’s syndrome. Full article
(This article belongs to the Special Issue Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges)
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19 pages, 10799 KiB  
Article
Characterization of the Endometrial MSC Marker Ectonucleoside Triphosphate Diphosphohydrolase-2 (NTPDase2/CD39L1) in Low- and High-Grade Endometrial Carcinomas: Loss of Stromal Expression in the Invasive Phenotypes
by Aitor Rodríguez-Martínez, Carla Trapero, August Vidal, Josep Maria Piulats, Inmaculada Gómez de Aranda, Jean Sévigny, Maria Eulàlia Fernández-Montolí, Jordi Ponce, Xavier Matias-Guiu and Mireia Martín-Satué
J. Pers. Med. 2021, 11(5), 331; https://doi.org/10.3390/jpm11050331 - 22 Apr 2021
Cited by 3 | Viewed by 2149
Abstract
Ectonucleoside triphosphate diphosphohydrolase-2 (NTPDase2/CD39L1) has been described in human non-pathological endometrium in both epithelial and stromal components without changes along the cycle. It was identified as a stromal marker of basalis. In the present study, we aimed to evaluate NTPDase2 distribution, using immunolabeling [...] Read more.
Ectonucleoside triphosphate diphosphohydrolase-2 (NTPDase2/CD39L1) has been described in human non-pathological endometrium in both epithelial and stromal components without changes along the cycle. It was identified as a stromal marker of basalis. In the present study, we aimed to evaluate NTPDase2 distribution, using immunolabeling and in situ enzyme activity approaches, in endometrial carcinoma (EC) at different tumor grades. NTPDase2 was present in tumor epithelial EC cells, as in the non-pathological endometria, but the expression underwent changes in subcellular distribution and also tended to decrease with the tumor grade. In stroma, NTPDase2 was identified exclusively at the tumor-myometrial junction but this expression was lost in tumors of invasive phenotype. We have also identified in EC samples the presence of the perivascular population of endometrial mesenchymal stem cells (eMSCs) positive for sushi domain containing 2 (SUSD2) and for NTPDase2, already described in non-tumoral endometrium. Our results point to NTPDase2 as a histopathological marker of tumor invasion in EC, with diagnostic relevance especially in cases of EC coexisting with other endometrial disorders, such as adenomyosis, which occasionally hampers the assessment of tumor invasion parameters. Full article
(This article belongs to the Special Issue Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges)
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19 pages, 5543 KiB  
Article
Comparing the Effect of TGF-β Receptor Inhibition on Human Perivascular Mesenchymal Stromal Cells Derived from Endometrium, Bone Marrow and Adipose Tissues
by Shanti Gurung, Daniela Ulrich, Marian Sturm, Anna Rosamilia, Jerome A. Werkmeister and Caroline E. Gargett
J. Pers. Med. 2020, 10(4), 261; https://doi.org/10.3390/jpm10040261 - 01 Dec 2020
Cited by 7 | Viewed by 2283
Abstract
Rare perivascular mesenchymal stromal cells (MSCs) with therapeutic properties have been identified in many tissues. Their rarity necessitates extensive in vitro expansion, resulting in spontaneous differentiation, cellular senescence and apoptosis, producing therapeutic products with variable quality and decreased potency. We previously demonstrated that [...] Read more.
Rare perivascular mesenchymal stromal cells (MSCs) with therapeutic properties have been identified in many tissues. Their rarity necessitates extensive in vitro expansion, resulting in spontaneous differentiation, cellular senescence and apoptosis, producing therapeutic products with variable quality and decreased potency. We previously demonstrated that A83-01, a transforming growth factor beta (TGF-β) receptor inhibitor, maintained clonogenicity and promoted the potency of culture-expanded premenopausal endometrial MSCs using functional assays and whole-transcriptome sequencing. Here, we compared the effects of A83-01 on MSCs derived from postmenopausal endometrium, menstrual blood, placenta decidua-basalis, bone marrow and adipose tissue. Sushi-domain-containing-2 (SUSD2+) and CD34+CD31CD45 MSCs were isolated. Expanded MSCs were cultured with or without A83-01 for 7 days and assessed for MSC properties. SUSD2 identified perivascular cells in the placental decidua-basalis, and their maternal origin was validated. A83-01 promoted MSC proliferation from all sources except bone marrow and only increased SUSD2 expression and prevented apoptosis in MSCs from endometrial-derived tissues. A83-01 only improved the cloning efficiency of postmenopausal endometrial MSCs (eMSCs), and expanded adipose tissue MSCs (adMSCs) underwent significant senescence, which was mitigated by A83-01. MSCs derived from bone marrow (bmMSCs) were highly apoptotic, but A83-01 was without effect. A83-01 maintained the function and phenotype in MSCs cultured from endometrial, but not other, tissues. Our results also demonstrated that cellular SUSD2 expression directly correlates with the functional phenotype. Full article
(This article belongs to the Special Issue Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges)
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Review

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28 pages, 3907 KiB  
Review
Modeling Endometrium Biology and Disease
by Nina Maenhoudt, Amber De Moor and Hugo Vankelecom
J. Pers. Med. 2022, 12(7), 1048; https://doi.org/10.3390/jpm12071048 - 27 Jun 2022
Cited by 10 | Viewed by 4250
Abstract
The endometrium, lining the uterine lumen, is highly essential for human reproduction. Its exceptional remodeling plasticity, including the transformation process to welcome and nest the embryo, is not well understood. Lack of representative and reliable study models allowing the molecular and cellular mechanisms [...] Read more.
The endometrium, lining the uterine lumen, is highly essential for human reproduction. Its exceptional remodeling plasticity, including the transformation process to welcome and nest the embryo, is not well understood. Lack of representative and reliable study models allowing the molecular and cellular mechanisms underlying endometrium development and biology to be deciphered is an important hurdle to progress in the field. Recently, powerful organoid models have been developed that not only recapitulate endometrial biology such as the menstrual cycle, but also faithfully reproduce diseases of the endometrium such as endometriosis. Moreover, single-cell profiling endeavors of the endometrium in health and disease, and of derived organoids, start to provide deeper insight into cellular complexity and expression specificities, and in resulting tissue processes. This granular portrayal will not only help in understanding endometrium biology and disease, but also in pinning down the tissue’s stem cells, at present not yet conclusively defined. Here, we provide a general overview of endometrium development and biology, and the efforts of modeling both the healthy tissue, as well as its key diseased form of endometriosis. The future of modeling and deciphering this key tissue, hidden inside the womb, looks bright. Full article
(This article belongs to the Special Issue Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges)
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17 pages, 1351 KiB  
Review
The Role of Endometrial Stem/Progenitor Cells in Recurrent Reproductive Failure
by Hannan Al-Lamee, Christopher J. Hill, Florence Turner, Thuan Phan, Andrew J. Drakeley, Dharani K. Hapangama and Nicola Tempest
J. Pers. Med. 2022, 12(5), 775; https://doi.org/10.3390/jpm12050775 - 11 May 2022
Cited by 5 | Viewed by 3449
Abstract
Recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL), collectively referred to as recurrent reproductive failure (RRF), are both challenging conditions with many unanswered questions relating to causes and management options. Both conditions are proposed to be related to an aberrant endometrial microenvironment, [...] Read more.
Recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL), collectively referred to as recurrent reproductive failure (RRF), are both challenging conditions with many unanswered questions relating to causes and management options. Both conditions are proposed to be related to an aberrant endometrial microenvironment, with different proposed aetiologies related to a restrictive or permissive endometrium for an invading embryo. The impressive regenerative capacity of the human endometrium has been well-established and has led to the isolation and characterisation of several subtypes of endometrial stem/progenitor cells (eSPCs). eSPCs are known to be involved in the pathogenesis of endometrium-related disorders (such as endometriosis) and have been proposed to be implicated in the pathogenesis of RRF. This review appraises the current knowledge of eSPCs, and their involvement in RRF, highlighting the considerable unknown aspects in this field, and providing avenues for future research to facilitate much-needed advances in the diagnosis and management of millions of women suffering with RRF. Full article
(This article belongs to the Special Issue Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges)
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15 pages, 2104 KiB  
Review
A Revised Stem Cell Theory for the Pathogenesis of Endometriosis
by Tetsuo Maruyama
J. Pers. Med. 2022, 12(2), 216; https://doi.org/10.3390/jpm12020216 - 04 Feb 2022
Cited by 15 | Viewed by 5368
Abstract
During the past decade, a stem cell-based hypothesis has emerged (among many others) to explain the pathogenesis of endometriosis. The initial hypothesis proposed that endometriosis arose from a single or a few specific cells with stem cell properties, including self-renewal and multi-lineage cell [...] Read more.
During the past decade, a stem cell-based hypothesis has emerged (among many others) to explain the pathogenesis of endometriosis. The initial hypothesis proposed that endometriosis arose from a single or a few specific cells with stem cell properties, including self-renewal and multi-lineage cell differentiation. The origins of the endometriosis-initiating stem cells were thought to be the bone marrow, uterine endometrium, and other tissues. Based on the implantation or metastatic theory in combination with the initial stem cell theory, one or a few multipotent stem/progenitor cells present in the eutopic endometrium or bone marrow translocate to ectopic sites via fallopian tubes during menstruation, vasculolymphatic routes, or through direct migration and invasion. Subsequently, they give rise to endometriotic lesions followed by differentiation into various cell components of endometriosis, including glandular and stromal cells. Recent somatic mutation analyses of deep infiltrating endometriosis, endometrioma, and eutopic normal endometrium using next-generation sequencing techniques have redefined the stem cell theory. It is now proposed that stem/progenitor cells of at least two different origins—epithelium and stroma—sequentially, differentially, but coordinately contribute to the genesis of endometriosis. The dual stem cell theory on how two (or more) stem/progenitor cells differentially and coordinately participate in the establishment of endometriotic lesions remains to be elucidated. Furthermore, the stem/progenitor cells involved in this theory also remain to be identified. Given that the origin of endometriosis is eutopic endometrium, the candidate cells for endometriotic epithelium-initiating cells are likely to be endometrial epithelial cells positive for either N-cadherin or SSEA-1 or both. The candidate cells for endometriotic stroma-initiating cells may be endometrial mesenchymal stem cells positive for SUSD2. Endometrial side population cells are also a possible candidate because they contain unipotent or multipotent cells capable of behaving as endometrial epithelial and stromal stem/progenitor cells. Full article
(This article belongs to the Special Issue Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges)
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17 pages, 1026 KiB  
Review
Making More Womb: Clinical Perspectives Supporting the Development and Utilization of Mesenchymal Stem Cell Therapy for Endometrial Regeneration and Infertility
by Michael Strug and Lusine Aghajanova
J. Pers. Med. 2021, 11(12), 1364; https://doi.org/10.3390/jpm11121364 - 14 Dec 2021
Cited by 14 | Viewed by 5118
Abstract
The uterus is a homeostatic organ, unwavering in the setting of monthly endometrial turnover, placental invasion, and parturition. In response to ovarian steroid hormones, the endometrium autologously prepares for embryo implantation and in its absence will shed and regenerate. Dysfunctional endometrial repair and [...] Read more.
The uterus is a homeostatic organ, unwavering in the setting of monthly endometrial turnover, placental invasion, and parturition. In response to ovarian steroid hormones, the endometrium autologously prepares for embryo implantation and in its absence will shed and regenerate. Dysfunctional endometrial repair and regeneration may present clinically with infertility and abnormal menses. Asherman’s syndrome is characterized by intrauterine adhesions and atrophic endometrium, which often impacts fertility. Clinical management of infertility associated with abnormal endometrium represents a significant challenge. Endometrial mesenchymal stem cells (MSC) occupy a perivascular niche and contain regenerative and immunomodulatory properties. Given these characteristics, mesenchymal stem cells of endometrial and non-endometrial origin (bone marrow, adipose, placental) have been investigated for therapeutic purposes. Local administration of human MSC in animal models of endometrial injury reduces collagen deposition, improves angiogenesis, decreases inflammation, and improves fertility. Small clinical studies of autologous MSC administration in infertile women with Asherman’s Syndrome suggested their potential to restore endometrial function as evidenced by increased endometrial thickness, decreased adhesions, and fertility. The objective of this review is to highlight translational and clinical studies investigating the use of MSC for endometrial dysfunction and infertility and to summarize the current state of the art in this promising area. Full article
(This article belongs to the Special Issue Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges)
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21 pages, 45051 KiB  
Review
Endometrial SUSD2+ Mesenchymal Stem/Stromal Cells in Tissue Engineering: Advances in Novel Cellular Constructs for Pelvic Organ Prolapse
by David M. Z. B. Hennes, Anna Rosamilia, Jerome A. Werkmeister, Caroline E. Gargett and Shayanti Mukherjee
J. Pers. Med. 2021, 11(9), 840; https://doi.org/10.3390/jpm11090840 - 26 Aug 2021
Cited by 8 | Viewed by 9795
Abstract
Cellular therapy is an emerging field in clinical and personalised medicine. Many adult mesenchymal stem/progenitor cells (MSC) or pluripotent derivatives are being assessed simultaneously in preclinical trials for their potential treatment applications in chronic and degenerative human diseases. Endometrial mesenchymal stem/progenitor cells (eMSC) [...] Read more.
Cellular therapy is an emerging field in clinical and personalised medicine. Many adult mesenchymal stem/progenitor cells (MSC) or pluripotent derivatives are being assessed simultaneously in preclinical trials for their potential treatment applications in chronic and degenerative human diseases. Endometrial mesenchymal stem/progenitor cells (eMSC) have been identified as clonogenic cells that exist in unique perivascular niches within the uterine endometrium. Compared with MSC isolated from other tissue sources, such as bone marrow and adipose tissue, eMSC can be extracted through less invasive methods of tissue sampling, and they exhibit improvements in potency, proliferative capacity, and control of culture-induced differentiation. In this review, we summarize the potential cell therapy and tissue engineering applications of eMSC in pelvic organ prolapse (POP), emphasising their ability to exert angiogenic and strong immunomodulatory responses that improve tissue integration of novel surgical constructs for POP and promote vaginal tissue healing. Full article
(This article belongs to the Special Issue Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges)
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11 pages, 1318 KiB  
Review
The New Era of Three-Dimensional Histoarchitecture of the Human Endometrium
by Manako Yamaguchi, Kosuke Yoshihara, Nozomi Yachida, Kazuaki Suda, Ryo Tamura, Tatsuya Ishiguro and Takayuki Enomoto
J. Pers. Med. 2021, 11(8), 713; https://doi.org/10.3390/jpm11080713 - 25 Jul 2021
Cited by 7 | Viewed by 2486
Abstract
The histology of the endometrium has traditionally been established by observation of two-dimensional (2D) pathological sections. However, because human endometrial glands exhibit coiling and branching morphology, it is extremely difficult to obtain an entire image of the glands by 2D observation. In recent [...] Read more.
The histology of the endometrium has traditionally been established by observation of two-dimensional (2D) pathological sections. However, because human endometrial glands exhibit coiling and branching morphology, it is extremely difficult to obtain an entire image of the glands by 2D observation. In recent years, the development of three-dimensional (3D) reconstruction of serial pathological sections by computer and whole-mount imaging technology using tissue clearing methods with high-resolution fluorescence microscopy has enabled us to observe the 3D histoarchitecture of tissues. As a result, 3D imaging has revealed that human endometrial glands form a plexus network in the basalis, similar to the rhizome of grass, whereas mouse uterine glands are single branched tubular glands. This review summarizes the relevant literature on the 3D structure of mouse and human endometrium and discusses the significance of the rhizome structure in the human endometrium and the expected role of understanding the 3D tissue structure in future applications to systems biology. Full article
(This article belongs to the Special Issue Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges)
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12 pages, 1026 KiB  
Review
Endometrial Perivascular Progenitor Cells and Uterus Regeneration
by Shiyuan Li and Lijun Ding
J. Pers. Med. 2021, 11(6), 477; https://doi.org/10.3390/jpm11060477 - 27 May 2021
Cited by 16 | Viewed by 3678
Abstract
Ovarian steroid-regulated cyclical regeneration of the endometrium is crucial for endometrial receptivity and embryo implantation, and it is dependent on the dynamic remodeling of the endometrial vasculature. Perivascular cells, including pericytes surrounding capillaries and microvessels and adventitial cells located in the outermost layer [...] Read more.
Ovarian steroid-regulated cyclical regeneration of the endometrium is crucial for endometrial receptivity and embryo implantation, and it is dependent on the dynamic remodeling of the endometrial vasculature. Perivascular cells, including pericytes surrounding capillaries and microvessels and adventitial cells located in the outermost layer of large vessels, show properties of mesenchymal stem cells, and they are thus promising candidates for uterine regeneration. In this review, we discuss the structure and functions of the endometrial blood vasculature and their roles in endometrial regeneration, the main biomarkers and characteristics of perivascular cells in the endometrium, and stem cell-based angiogenetic therapy for Asherman’s syndrome. Full article
(This article belongs to the Special Issue Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges)
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