title: Exosomes derived from endometriotic stromal cells have enhanced angiogenic effects in vitro.
abstract: Our objective has been to establish a pro-angiogenic role for exosomes in endometriosis and to determine whether a differential expression profile of cellular and exosomal microRNAs (miRNAs) exists in endometriosis. We performed an in vitro study of human primary endometrial stromal cells (ESCs) and human umbilical vein endothelial cells (HUVECs). We isolated and characterized exosomes from ESCs from five endometriosis patients and five phase-matched controls. Exosomes were characterized by transmission electron microscopy and NanoSight technology. MiRNA was assessed by deep sequencing and reverse transcription with quantitative polymerase chain reaction. Exosome uptake studies were achieved by means of confocal microscopy. The pro-angiogenic experiments were executed by treating HUVECs with ESC-derived exosomes. We observed differential profiles of exosomal miRNA expression between exosomes derived from endometriosis lesion cells and diseased eutopic stromal cells compared with exosomes derived from control ESCs. We also demonstrated autocrine cellular uptake of exosomes and paracrine functional angiogenic effects of exosomes on HUVECs. The results of this study support the hypothesis that exosomes derived from ESCs play autocrine/paracrine roles in the development of endometriosis, potentially modulating angiogenesis. The broader clinical implications are that Sampson's theory of retrograde menstruation possibly encompasses the finding that exosomes work as intercellular communication modulators in endometriosis.
authors: Department of Obstetrics and Gynecology, Morehouse School of Medicine, 720 Westview Drive, SW, Atlanta, GA 30310, USA. dharp@msm.edu.
authors: Djana
authors: D
authors: Harp
authors: Department of Obstetrics and Gynecology, Morehouse School of Medicine, 720 Westview Drive, SW, Atlanta, GA 30310, USA.
authors: Adel
authors: A
authors: Driss
authors: Department of Obstetrics and Gynecology, Morehouse School of Medicine, 720 Westview Drive, SW, Atlanta, GA 30310, USA.
authors: Sharifeh
authors: S
authors: Mehrabi
authors: Department of Obstetrics and Gynecology, Morehouse School of Medicine, 720 Westview Drive, SW, Atlanta, GA 30310, USA.
authors: Indrajit
authors: I
authors: Chowdhury
authors: Department of Obstetrics and Gynecology, Morehouse School of Medicine, 720 Westview Drive, SW, Atlanta, GA 30310, USA.
authors: Wei
authors: W
authors: Xu
authors: Cardiovascular Research Institute, Morehouse School of Medicine, 720 Westview Drive, SW, Atlanta, GA 30310, USA.|Department of Physiology, Morehouse School of Medicine, 720 Westview Drive, SW, Atlanta, GA 30310, USA.
authors: Dong
authors: D
authors: Liu
authors: Cardiovascular Research Institute, Morehouse School of Medicine, 720 Westview Drive, SW, Atlanta, GA 30310, USA.|Department of Physiology, Morehouse School of Medicine, 720 Westview Drive, SW, Atlanta, GA 30310, USA.
authors: Minerva
authors: M
authors: Garcia-Barrio
authors: Department of Obstetrics and Gynecology, Wake Forest School of Medicine, 1 Medical Center Boulevard, Winston-Salem, NC 27157, USA.
authors: Robert N
authors: RN
authors: Taylor
authors: Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
authors: Bert
authors: B
authors: Gold
authors: Georgia State University, P.O. Box 3965, Atlanta, GA 30302, USA.
authors: Samantha
authors: S
authors: Jefferson
authors: Department of Gynecology & Obstetrics, Emory University School of Medicine, 1639 Pierce Dr., WMB 4303, Atlanta, GA 30322, USA.
authors: Neil
authors: N
authors: Sidell
authors: Department of Obstetrics and Gynecology, Morehouse School of Medicine, 720 Westview Drive, SW, Atlanta, GA 30310, USA.|Department of Physiology, Morehouse School of Medicine, 720 Westview Drive, SW, Atlanta, GA 30310, USA.
authors: Winston
authors: W
authors: Thompson
mesh_terms: D000328:Adult; D019898:Autocrine Communication; D003470:Culture Media / Q000737:chemistry; D004715:Endometriosis / Q000473:pathology*; D055354:Exosomes / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D003470:Culture Media; D035683:MicroRNAs
keywords: Angiogenesis; Endometrial stromal cells; Exosomes; Infertility; MicroRNA