Chemoattraction of bone marrow-derived stem cells towards human endometrial stromal cells is mediated by estradiol regulated CXCL12 and CXCR4 expression
Open accessAbstract
Bone marrow derived cells engraft to the uterine endometrium and contribute to endometriosis. The mechanism by which these cells are mobilized and directed to the endometrium has not been previously characterized. We demonstrate that human endometrial stromal cells (hESCs) produce the chemokine CXCL12 and that bone marrow cells (BMCs) express the CXCL12 receptor, CXCR4. Treatment with physiological levels of estradiol (E2) induced both CXCL12 and CXCR4 expression in hESCs and BMCs, respectively. BMCs migrated towards hESCs conditioned media; a CXCR4 antagonist blocked migration indicating that CXCL12 acting through its receptor, CXCR4, is necessary for chemoattraction of BM cells to human endometrial cells. E2 increased both CXCL12 expression in endometrial cells and CXCR4 expression in BM cells, further enhancing chemoattraction. E2 induced CXCL12/CXCR4 expression in endometrium and BM, respectively, drives migration of stem cells to the endometrium. The E2-CXCL12/CXCR4 signaling pathway may be useful in determining treatments for endometrial disorders, and may be antagonized to block stem cell migration to endometriosis.
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SDF-1 plays a critical role in recruiting bone marrow derived stem cells to endometrium and ectopic endometrium.
“Incidentally or not, SDF-1 plays a critical role in recruiting bone marrow derived stem cells (BMDSCs) to endometrium and ectopic endometrium [90,91].”
From The Pathogenesis of Adenomyosis vis-à-vis Endometriosis (2020) · cites this paper as [91]
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Eliminating Hormones With Orally Active Gonadotropin-releasing Hormone Antagonists
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ENDOCELL-Seud: a Delphi protocol to harmonise methods in endometrial cell culturing
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Additional file 1 of All-in-one smart dressing for simultaneous angiogenesis and neural regeneration
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Genital Tract and Circulating CD8+ T Cell Phenotypes Vary Across the Menstrual Cycle
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- Authors
- Wang, X., Mamillapalli, R., Mutlu, L., Du, H., & Taylor, H. S.
- Affiliations
- Yale University (US)
- Corresponding author
- Mamillapalli, Ramanaiah
- Venue
- Stem Cell Research
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 15
- Issue
- 1
- Pages
- 14-22
- ISSN
- 1873-5061 (ISSN-L)
- PMC
- PMC5001152
- OpenAlex
- W2036591541
- Cited by
- 93
- References
- 35
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 8 · 2022: 13 · 2021: 14 · 2020: 9 · 2019: 5 · 2018: 11 · 2017: 8 · 2016: 6 · 2015: 4
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Stem Cell Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD076422)
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- endometriosis, bone marrow-derived stem cells, endometrial stromal cells, CXCL12, CXCR4, estradiol, chemotaxis, stem cell migration, chemokine signaling, endometrium
- MeSH terms
- Animals, Bone Marrow Cells, Chemotactic Factors, Chemotaxis, Endometrium, Estradiol, Female, Flow Cytometry, Humans, Mice, Inbred C57BL, Progesterone, Stem Cells, Uterus, Blotting, Western, Immunophenotyping, Culture Media, Conditioned, Stromal Cells, Leukocyte Common Antigens, Receptors, CXCR4, Chemokine CXCL12
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