PMID- 25957946 OWN - NLM STAT- MEDLINE DCOM- 20160425 LR - 20181113 IS - 1876-7753 (Electronic) IS - 1873-5061 (Print) IS - 1873-5061 (Linking) VI - 15 IP - 1 DP - 2015 Jul TI - Chemoattraction of bone marrow-derived stem cells towards human endometrial stromal cells is mediated by estradiol regulated CXCL12 and CXCR4 expression. PG - 14-22 LID - S1873-5061(15)00046-X [pii] LID - 10.1016/j.scr.2015.04.004 [doi] AB - 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. CI - Copyright (c) 2015. Published by Elsevier B.V. FAU - Wang, Xiuli AU - Wang X AD - Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA. FAU - Mamillapalli, Ramanaiah AU - Mamillapalli R AD - Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA. Electronic address: ramana.mamillapalli@yale.edu. FAU - Mutlu, Levent AU - Mutlu L AD - Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA. FAU - Du, Hongling AU - Du H AD - Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA. FAU - Taylor, Hugh S AU - Taylor HS AD - Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA. LA - eng GR - R01 HD076422/HD/NICHD NIH HHS/United States PT - Journal Article DEP - 20150424 PL - England TA - Stem Cell Res JT - Stem cell research JID - 101316957 RN - 0 (Chemokine CXCL12) RN - 0 (Chemotactic Factors) RN - 0 (Culture Media, Conditioned) RN - 0 (Receptors, CXCR4) RN - 4G7DS2Q64Y (Progesterone) RN - 4TI98Z838E (Estradiol) RN - EC 3.1.3.48 (Leukocyte Common Antigens) SB - IM MH - Animals MH - Blotting, Western MH - Bone Marrow Cells/*cytology MH - Chemokine CXCL12/*metabolism MH - Chemotactic Factors/*pharmacology MH - Chemotaxis/drug effects MH - Culture Media, Conditioned/pharmacology MH - Endometrium/*cytology MH - Estradiol/*pharmacology MH - Female MH - Flow Cytometry MH - Humans MH - Immunophenotyping MH - Leukocyte Common Antigens/metabolism MH - Mice, Inbred C57BL MH - Progesterone/pharmacology MH - Receptors, CXCR4/*metabolism MH - Stem Cells/*cytology/drug effects/metabolism MH - Stromal Cells MH - Uterus/cytology PMC - PMC5001152 MID - NIHMS809416 EDAT- 2015/05/11 06:00 MHDA- 2016/04/26 06:00 PMCR- 2016/08/26 CRDT- 2015/05/11 06:00 PHST- 2015/01/14 00:00 [received] PHST- 2015/04/04 00:00 [revised] PHST- 2015/04/18 00:00 [accepted] PHST- 2015/05/11 06:00 [entrez] PHST- 2015/05/11 06:00 [pubmed] PHST- 2016/04/26 06:00 [medline] PHST- 2016/08/26 00:00 [pmc-release] AID - S1873-5061(15)00046-X [pii] AID - 10.1016/j.scr.2015.04.004 [doi] PST - ppublish SO - Stem Cell Res. 2015 Jul;15(1):14-22. doi: 10.1016/j.scr.2015.04.004. Epub 2015 Apr 24.