Establishment of Immortalized Human Endometriotic Stromal Cell Line from Ectopic Lesion of a Patient with Endometriosis

Endometriosis is an estrogen-dependent inflammatory disease characterized by the growth of endometrial-like tissues containing endometrial stromal cells and glandular epithelium outside the uterine cavity. An insufficient response to progesterone contributes to disease progression and systemic inflammation during the pathogenesis of endometriosis. Patients with endometriosis usually experience painful symptoms, dysmenorrhea, and infertility, which contribute to a significant reduction in their quality of life. To determine the possible molecular mechanisms of endometriosis and explore novel therapeutic targets, we derived primary human ovarian endometriotic stromal cells (hOESCs) from a patient of reproductive age with ovarian endometriosis. In this study, we successfully established immortalized human ovarian endometriotic stromal cell lines (ihOESCs) using primary stromal cells obtained from endometriotic lesions to overcome short lifespan and growth inhibition. Immortalization of hOESCs with human telomerase reverse transcriptase (hTERT) transfection led to cells that maintained a proliferative state under passage culture conditions without mutagenesis during cellular senescence. The morphology and karyotype of ihOESCs were unchanged compared with those of hOESCs. Moreover, ihOESCs were continuously positive for vimentin and negative for E-cadherin expression. Following decidual stimuli and inflammatory responses, both hOESCs and ihOESCs sensitively express decidualization markers and proinflammatory cytokines. Collectively, we characterized ihOESCs to maintain their phenotypic and functional properties with a longer lifespan and normal physiological responses than those of hOESCs. These immortalized cells could aid in a detailed understanding of the pathological mechanisms of endometriosis. Similar content being viewed by others

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Also, this research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI22C1424). Author information Authors and Affiliations Contributions The authors’ responsibilities were as follows: GS, SY, and WL conceived and designed the culture experiments, the cell culture methodology, and all other experiments; DS, HP, GA, SP, DWH, SJP, and HSK collected experimental samples and conducted all experiments; HSK, WL, SY, and GS analyzed and interpreted the data and contributed to the development of the manuscript. All authors contributed to its critical review and agreed on the final version. Corresponding authors Ethics declarations Ethics Approval and Consent to Participate All experimental and surgical procedures in this study were compliant with the Guide for Care and Use of Experimental Animals in Teaching and Research and were approved by the Institutional Animal Care and Use Committee of Korea University and the Institutional Review Board of Seoul National University Hospital in advance (No. 2005-204-1127). All patients gave their written informed consent for this study. Consent for Publication Not applicable. Conflict of Interest The authors declare no competing interests. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Son, D., Park, H., An, G. et al. Establishment of Immortalized Human Endometriotic Stromal Cell Line from Ectopic Lesion of a Patient with Endometriosis. Reprod. Sci. 30, 2703–2714 (2023). https://doi.org/10.1007/s43032-023-01225-9 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-023-01225-9