Bone marrow stem cells do not contribute to endometrial cell lineages in chimeric mouse models
Open accessAbstract
Studies from five independent laboratories conclude that bone marrow stem cells transdifferentiate into endometrial stroma, epithelium, and endothelium. We investigated the nature of bone marrow-derived cells in the mouse endometrium by reconstituting irradiated wild type recipients with bone marrow containing transgenic mTert-green fluorescent protein (GFP) or chicken β-actin (Ch β-actin)-GFP reporters. mTert-GFP is a telomerase marker identifying hematopoietic stem cells and subpopulations of epithelial, endothelial, and immune cells in the endometrium. Ch β-actin-GFP is a ubiquitous reporter previously used to identify bone marrow-derived cells in the endometrium. Confocal fluorescence microscopy for GFP and markers of endometrial and immune cells were used to characterize bone marrow-derived cells in the endometrium of transplant recipients. No evidence of GFP+ bone marrow-derived stroma, epithelium, or endothelium was observed in the endometrium of mTert-GFP or Ch β-actin-GFP recipients. All GFP+ cells detected in the endometrium were immune cells expressing the pan leukocyte marker CD45, including CD3+ T cells and F4/80+ macrophages. Further examination of the Ch β-actin-GFP transplant model revealed that bone marrow-derived F4/80+ macrophages immunostained weakly for CD45. These macrophages were abundant in the stroma, infiltrated the epithelial and vascular compartments, and could easily be mistaken for bone marrow-derived endometrial cells. We conclude that it is unlikely that bone marrow cells are able to transdifferentiate into endometrial stroma, epithelium, and endothelium. This result has important therapeutic implications, as the expectation that bone marrow stem cells contribute directly to endometrial regeneration is shaping strategies designed to regenerate endometrium in Asherman's syndrome and to control aberrant endometrial growth in endometriosis.
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Macrophages secrete vimentin and are weakly positive for leukocyte marker CD45, so they could easily be mistaken for endometrial cells.
“As macrophages secrete vimentin and are weakly positive for leukocyte marker CD45, they could easily be mistaken for endometrial cells (Mor-Vaknin et al., 2003;Ong et al., 2018).”
From Endometriosis and nuclear receptors (2019) · cites this paper as Ong et al., 2018
The Results section on low CD45 immunoreactivity reports that endometrial macrophages stain weakly for CD45. The Discussion says this can lead to their misidentification as non-immune, bone marrow-derived endometrial cells. Our copy does not say that macrophages secrete vimentin. (LLM, conf=0.88)
Experimental — accuracy not yet measuredA study of a chimeric irradiated mouse model transplanted with immunofluorescent labeled marrow showed that bone marrow-derived cells that infiltrate into the epithelial and vascular compartments may be F4/80(+) macrophages.
“Recently, a study of a chimeric irradiated mouse model transplanted with immunofluorescent labeled marrow showed that bone marrow-derived cells that infiltrate into the epithelial and vascular compartments may be F4/80(+) macrophages (Ong et al., 2018).”
From Endometriosis and nuclear receptors (2019) · cites this paper as Ong et al., 2018
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- Authors
- Ong, Y. R., Cousins, F. L., Yang, X., Mushafi, A. A. A. A., Breault, D. T., Gargett, C. E., & Deane, J. A.
- Affiliations
- Hudson Institute of Medical Research (AU)
- Boston Children's Hospital (US)
- Corresponding author
- Deane, James A.
- ORCID
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-10-04
- Volume
- 36
- Issue
- 1
- Pages
- 91-102
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W2753940896
- Cited by
- 56
- References
- 51
- Citations by year
- 2025: 4 · 2024: 4 · 2023: 5 · 2022: 10 · 2021: 13 · 2020: 6 · 2019: 3 · 2018: 11
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Stem Cells (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council (1085235, 1042298)
- Victorian Government's Operational Infrastructure Support Program
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- bone marrow-derived stem cells, endometrium, transdifferentiation, chimeric mouse model, endometrial stroma, endometrial epithelium, F4/80+ macrophages, CD45, endometrial regeneration, intrauterine adhesions, endometriosis, hematopoietic stem cells
- MeSH terms
- Animals, Bone Marrow Cells, Cell Differentiation, Disease Models, Animal, Bone Marrow Transplantation, Cell Lineage, Mice
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