title: Chemoattraction of bone marrow-derived stem cells towards human endometrial stromal cells is mediated by estradiol regulated CXCL12 and CXCR4 expression.
abstract: 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.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA. Electronic address: ramana.mamillapalli@yale.edu.
authors.forename: Ramanaiah
authors.initials: R
authors.lastname: Mamillapalli
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Levent
authors.initials: L
authors.lastname: Mutlu
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Hongling
authors.initials: H
authors.lastname: Du
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Taylor
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002630:Chemotactic Factors / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004717:Endometrium / Q000166:cytology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008810:Mice, Inbred C57BL; D011374:Progesterone / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D017154:Stromal Cells; D014599:Uterus / Q000166:cytology
chemical_list: D054377:Chemokine CXCL12; D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D019718:Receptors, CXCR4; D011374:Progesterone; D004958:Estradiol; D017493:Leukocyte Common Antigens