CoChat
Sign Up
Cited by 91Mesenchymal stem cell researchHematopoietic Stem Cell TransplantationPluripotent Stem Cells Research

Mesenchymal stem/stromal cells in post-menopausal endometrium

Ulrich, D., Tan, K. S., Deane, J., Schwab, K., Cheong, A., Rosamilia, A., Gargett, C. E.·2014·Human Reproduction
DOI 10.1093/humrep/deu159
Open this paper in CoChat — free account

Abstract

STUDY QUESTION: Does post-menopausal endometrium contain mesenchymal stem/stromal cells (MSC) that have adult stem cell properties and can be prospectively isolated from a biopsy? SUMMARY ANSWER: Perivascular W5C5(+) cells isolated from post-menopausal endometrial biopsies displayed characteristic MSC properties of clonogenicity, multipotency and surface phenotype irrespective of whether the women were or were not pre-treated with estrogen to regenerate the endometrium. WHAT IS KNOWN ALREADY: Recently MSCs have been identified in human premenopausal endometrium, and can be prospectively isolated using a single marker, W5C5/SUSD2. STUDY DESIGN, SIZE, DURATION: Endometrial tissue of both the functional and basal layers, from 17 premenopausal (pre-MP) women, 19 post-menopausal (post-MP) women without hormonal treatment and 15 post-menopausal women on estrogen replacement therapy (post-MP+ E2), was collected through a prospective phase IV clinical trial over 2 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Post-menopausal women <65 years of age were treated with or without E2 for 6-8 weeks prior to tissue collection. Serum E2 levels were determined by estradiol immunoenzymatic assay. Endometrial tissue was obtained from women by biopsy (curettage) just prior to the hysterectomy. The effect of E2 on endometrial thickness and glandular and luminal epithelial height was determined using image analysis. Endometrial tissue was dissociated into single cell suspensions and MSC properties were examined in freshly isolated and short-term cultured, magnetic bead-purified W5C5(+) cells. MSC properties were assessed using clonogenicity, serial cloning, mesodermal differentiation in adipogenic, chondrogenic, osteogenic and myogenic induction culture media, and surface phenotype analysis by flow cytometry. Estrogen receptor α expression in W5C5(+) cells was examined using dual colour immunofluorescence. Vascularity was analysed using CD34 and alpha smooth muscle actin immunostaining and subsequent image analysis. MAIN RESULTS AND THE ROLE OF CHANCE: A small population of stromal cells with MSC properties was purified with the W5C5 antibody from post-menopausal endometrium, whether atrophic from low circulating estrogen or regenerated from systemic estrogen treatment, similar to premenopausal endometrium. The MSC derived from post-menopausal endometrium treated with or without E2 fulfilled the minimum MSC criteria: clonogenicity, surface phenotype (CD29(+), CD44(+), CD73(+), CD105(+), CD140b(+), CD146(+)) and multipotency. The post-menopausal endometrial MSCs also showed comparable properties to premenopausal eMSC with respect to self-renewal in vitro and W5C5 expression. The W5C5(+) cells were located perivascularly as expected and did not express estrogen receptor α. LIMITATIONS, REASONS FOR CAUTION: The properties of the MSC derived from post-menopausal endometrium were evaluated in vitro and their in vivo tissue reconstitution capacity has not been established as it has for premenopausal endometrial MSC. WIDER IMPLICATIONS OF THE FINDINGS: The endometrium is an accessible source of MSC obtainable with minimum morbidity that could be used for future clinical applications as a cell-based therapy. This study shows that menopausal women can access their endometrial MSC by a simple biopsy for use in autologous therapies, particularly if their endometrium has been regenerated by short-term E2 treatment, provided they have an intact uterus and are not contraindicated for short-term E2 treatment. Endometrial MSC in post-menopausal women possess key MSC properties and are a promising source of MSC independent of a woman's age. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the National Health and Medical Research Council (NHMRC) of Australia grant (1021126) (C.E.G., A.R.) and Senior Research Fellowship (1042298) (C.E.G.), Australian Gynaecological Endoscopic Society grant (A.R.) , Monash International Postgraduate Research Scholarship (DU), Australian Stem Cell Centre, South East Melbourne Alliance for Regenerative Therapies and Australian Stem Cell Centre top up scholarships (DU) and Victorian Government's Operational Infrastructure Support Program. Competing interests: AR receives Preceptorship fees from AMS, advisory board fees and sponsored study from Astellas, and conducts investigator led studies sponsored by AMS and Boston Scientific for other projects. TRIAL REGISTRATION NUMBER: CTNRN12610000563066.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/humrep/deu159

Cites

40 of 40 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • SUSD2(+) eMSCs are also ESR1-negative.

    “Similarly, SUSD2(+) eMSCs are also ESR1-negative (Ulrich et al., 2014).”

    From Endometriosis and nuclear receptors (2019) · cites this paper as Ulrich et al., 2014

    In “Location of W5C5 in post-menopausal endometrium” (p. 7), the authors report that none of the W5C5-positive cells expressed ERα, the protein encoded by ESR1, in post-menopausal tissue with or without estrogen treatment. This supports the claim for the cells studied, but does not establish ESR1 negativity for eMSCs generally, including those in premenopausal endometrium. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • In post-menopausal women, estradiol treatment increases the total number of SUSD2(+) eMSCs and the endometrial thickness proportionally.

    “In post-menopausal women, estradiol treatment increases the total number of SUSD2(+) eMSCs and the endometrial thickness proportionally (Ulrich et al., 2014).”

    From Endometriosis and nuclear receptors (2019) · cites this paper as Ulrich et al., 2014

    Experimental — accuracy not yet measured

  • Comparison of post-menopausal and premenopausal endometrial tissues revealed eMSCs with similar self-renewal capacity and expression of SUSD2.

    “Comparison of post-menopausal and premenopausal endometrial tissues revealed eMSCs with similar self-renewal capacity and expression of SUSD2 (Ulrich et al., 2014).”

    From Endometriosis and nuclear receptors (2019) · cites this paper as Ulrich et al., 2014

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Hickey M, Lau TM, Russell P, Fraser IS, Rogers PAW. Microvascular density in conditions of endometrial atrophy. Hum Reprod 1996; 11 :2009-2013.

Cited by

Sorted by citations

Related

Authors
Ulrich, D., Tan, K. S., Deane, J., Schwab, K., Cheong, A., Rosamilia, A., & Gargett, C. E.
Affiliations
  • Medical University of Graz (AT)
  • Hudson Institute of Medical Research (AU)
  • Monash Medical Centre (AU)
Corresponding author
Gargett, C. E.
ORCID
Venue
Human Reproduction
Publisher
Oxford University Press (OUP)
Published
2014-06-25
Volume
29
Issue
9
Pages
1895-1905
ISSN
  • 0268-1161 (ISSN-L)
  • 1460-2350
DOI
10.1093/humrep/deu159
OpenAlex
W2101479504
Cited by
91
References
40
Citations by year
2026: 1 · 2025: 5 · 2024: 12 · 2023: 7 · 2022: 7 · 2021: 11 · 2020: 12 · 2019: 7 · 2018: 9 · 2017: 6 · 2016: 11 · 2015: 3
FWCI
3.34
Type
journal article
Language
en
Open access
closed
Locations
  • Human Reproduction (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords
estrogen replacement therapy, endometrial regeneration, perivascular stromal cells, clonogenicity, multipotency, mesoderm differentiation, estrogen receptor alpha, endometrial vascularity, endometrial atrophy, endometrial biopsy
MeSH terms
Adult, Aged, Cell Differentiation, Cells, Cultured, Endometrium, Female, Humans, Middle Aged, Estrogen Replacement Therapy, Stromal Cells, Postmenopause, Cell Lineage, Mesenchymal Stem Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review