Side Population Cells in Human Adenomyotic Lesions Display Characteristics of Endometrial Stem Cells

Introduction: The precise etiology and physiopathology of ademyosis is still unknown. The aim of this research is to investigate if stem cells are found in adenomyosis and to characterize the role of adenomyotic lesion-derived side population (SP) cells in pathogenesis of adenomyosis. Methods: We recruited 31 women (range 37-48 years) treated by hysterectomy for adenomyosis. Adenomyotic samples were collected and The SP cells in the tissues were identified by flow cytometry. ATP-binding cassette transporter 2+ (ABCG2+) cells were isolated from human adenomyotic samples by magnetic activated cell sorting (MACS), further subjected to colony formation, induced differentiation in four conditions and mobility/invasion assay. The cell lines generated from ABCG2+ cells were analyzed by immunofluorescence, quantitative real-time PCR and western blot analysis. Results: The side population represents 1.59±0.48% of the total cell population in adenomyotic lesions. Cloning efficiency of the ABCG2+ cells was 11.27±1.74%. When co-cultured with endometrial cells, ABCG2+ cells differentiated into endometrium-like cells. Moreover, if 17β-estradiol was administrated to the co-culture system, a significantly higher efficiency of differentiation was detected (P<0.05). ABCG2+ cells in co-culture system displayed a higher efficiency of differentiation, compared to that in culture without feeder cells (p<0.05). The wound closure and transwell assays demonstrated that 17β-estradiol stimulates the migration/invasion of ABCG2+ cells in a dose-dependent manner, with a peak effect at a concentration of 10-8 M. Conclusions: The adenomyosis-derived ABCG2+ cells display stem cell-like properties and may be involved in the pathogenesis of adenomyosis.