Insights into Endometriosis Organoids Based on Uterine Tissue Engineering: A Mini-review

Zeinab Nurian, Nurian Z, Zeinan Nurian, Alireza Ebrahimzadeh‐Bideskan, Ebrahimzadeh A, Alireza Ebrahimzadeh, Fatemeh Alipour, Alipour F, Hengameh Dortaj, Dortaj H
Current stem cell research & therapy · 2025 · vol. 21(1) , pp. 1–10 · doi:10.2174/011574888x360426250529055140 · PMID:40491370 · W4411189154
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This review explores how uterine organoids and decellularized tissue scaffolds improve in vitro modeling of endometrial diseases, offering potential for drug screening and regenerative therapies.

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This mini-review discusses how uterine organoid-based and uterine tissue-engineering approaches are used to model diseases affecting the endometrium, contrasting traditional 2D monolayer cultures with 3D scaffold-free organoids and decellularized tissue scaffolds that better preserve native extracellular matrix features and hormone responsiveness. It reports that optimized decellularization protocols can generate intact uterine scaffolds and that implantation into animal models supports biocompatibility and regenerative potential, while organoid and scaffold refinements (including chemically defined matrices and microfluidic organ-on-a-chip platforms) are expected to improve uterus modeling and enable patient-derived, personalized disease studies and drug screening. A key limitation noted is that conventional 2D systems have reduced biological activity, reduced hormone responsiveness, and lack of ECM interaction, motivating the shift to more complex 3D platforms. This paper is centrally about endometriosis — it focuses on insights into endometriosis organoids and uterine tissue-engineering methods to model endometriosis-related biology.

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Abstract

Endometriosis is a chronic condition where tissue similar to the endometrium grows outside the uterus, affecting 5-10% of women and causing pelvic pain, painful periods, and infertility. Diseases of the endometrium, the lining of the uterus, can lead to a variety of reproductive health issues, including infertility, irregular bleeding, and endometrial cancer. Researchers have developed advanced in vitro systems using uterine organoids and decellularized tissue scaffolds to understand and model these diseases. The main limitations of traditional 2D monolayer cultures include reduced biological activity, reduced hormone responsiveness, and lack of interaction with ECM. Researchers have investigated 3D culture approaches to address these shortcomings, such as scaffold-free organoids and decellularized tissue scaffolds. Organoid systems can better recapitulate the cellular heterogeneity and physiological functions of the native endometrium. Decellularization protocols have been optimized to generate intact uterine scaffolds that preserve the structural and compositional features of the ECM. Implantation of these bioscaffolds into animal models demonstrated their biocompatibility and regenerative potential. Further refinements of organoid and scaffold technologies, including chemically defined matrices and organ-on-a-chip platforms, will improve our ability to model the uterus. Integration of these advanced in vitro models with patient-derived cells will enable personalized disease modeling and the development of targeted therapies. The combination of organoids, decellularized scaffolds, and microfluidic technologies holds great potential for exploring reproductive biology, drug screening, and developing regenerative therapies for uterine diseases and infertility.
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Abstract

Endometriosis is a chronic condition where tissue similar to the endometrium grows outside the uterus, affecting 5-10% of women and causing pelvic pain, painful periods, and infertility. Diseases of the endometrium, the lining of the uterus, can lead to a variety of reproductive health issues, including infertility, irregular bleeding, and endometrial cancer. Researchers have developed advanced in vitro systems using uterine organoids and decellularized tissue scaffolds to understand and model these diseases. The main limitations of traditional 2D monolayer cultures include reduced biological activity, reduced hormone responsiveness, and lack of interaction with ECM. Researchers have investigated 3D culture approaches to address these shortcomings, such as scaffold-free organoids and decellularized tissue scaffolds. Organoid systems can better recapitulate the cellular heterogeneity and physiological functions of the native endometrium. Decellularization protocols have been optimized to generate intact uterine scaffolds that preserve the structural and compositional features of the ECM. Implantation of these bioscaffolds into animal models demonstrated their biocompatibility and regenerative potential. Further refinements of organoid and scaffold technologies, including chemically defined matrices and organ-on-a-chip platforms, will improve our ability to model the uterus. Integration of these advanced in vitro models with patient-derived cells will enable personalized disease modeling and the development of targeted therapies. The combination of organoids, decellularized scaffolds, and microfluidic technologies holds great potential for exploring reproductive biology, drug screening, and developing regenerative therapies for uterine diseases and infertility.

Keywords

Endometriosis, organoid, uterus, tissue engineering, cell culture, ondometer. [1] Parasar, P.; Ozcan, P.; Terry, K.L. Endometriosis: Epidemiology, diagnosis and clinical management. Curr. Obstet. Gynecol. Rep., 2017, 6(1), 34-41. [http://dx.doi.org/10.1007/s13669-017-0187-1] [PMID: 29276652] [http://dx.doi.org/10.1007/s13669-017-0187-1] [PMID: 29276652] [2] Wu, J.; Lin, S.; Kong, S. Psychological stress and functional endometrial disorders: Update of mechanism insights. Front. Endocrinol. (Lausanne), 2021, 12, 690255. [http://dx.doi.org/10.3389/fendo.2021.690255] [PMID: 34413829] [http://dx.doi.org/10.3389/fendo.2021.690255] [PMID: 34413829] [3] Nijkang, N.P.; Anderson, L.; Markham, R.; Manconi, F. Endometrial polyps: Pathogenesis, sequelae and treatment. SAGE Open Med., 2019, 7, 2050312119848247. [http://dx.doi.org/10.1177/2050312119848247] [PMID: 31105939] [http://dx.doi.org/10.1177/2050312119848247] [PMID: 31105939] [4] Ring, K.L.; Mills, A.M.; Modesitt, S.C. Endometrial hyperplasia. Obstet. Gynecol., 2022, 140(6), 1061-1075. [PMID: 36357974] [PMID: 36357974] [5] Endometrial hyperplasia Seminars in Diagnostic Pathology; Mills, A.M.; Longacre, T.A., Eds.; Elsevier, 2010. [6] Morice, P.; Leary, A.; Creutzberg, C.; Abu-Rustum, N.; Darai, E. Endometrial cancer. Lancet, 2016, 387(10023), 1094-1108. [http://dx.doi.org/10.1016/S0140-6736(15)00130-0] [PMID: 26354523] [http://dx.doi.org/10.1016/S0140-6736(15)00130-0] [PMID: 26354523] [7] Ikhena, D.E.; Bulun, S.E. Literature review on the role of uterine fibroids in endometrial function. Reprod. Sci., 2018, 25(5), 635-643. [http://dx.doi.org/10.1177/1933719117725827] [PMID: 28826369] [http://dx.doi.org/10.1177/1933719117725827] [PMID: 28826369] [8] Sommers, S.C. Defining the pathology of endometrial hyperplasia, dysplasia and carcinoma. Pathol. Res. Pract., 1982, 174(3), 175-197. [http://dx.doi.org/10.1016/S0344-0338(82)80066-6] [PMID: 6292884] [http://dx.doi.org/10.1016/S0344-0338(82)80066-6] [PMID: 6292884] [9] Stringfellow, H.F.; Elliot, V.J. Endometrial metaplasia. Diagn. Histopathol., 2017, 23(7), 303-310. [http://dx.doi.org/10.1016/j.mpdhp.2017.05.006] [http://dx.doi.org/10.1016/j.mpdhp.2017.05.006] [10] Rafique, S.; Decherney, A.H. Medical management of endometriosis. Clin. Obstet. Gynecol., 2017, 60(3), 485-496. [http://dx.doi.org/10.1097/GRF.0000000000000292] [PMID: 28590310] [http://dx.doi.org/10.1097/GRF.0000000000000292] [PMID: 28590310] [11] Filby, C.E.; Wyatt, K.A.; Mortlock, S. Comparison of organoids from menstrual fluid and hormone-treated endometrium: Novel tools for gynecological research. J. Pers. Med., 2021, 11(12), 1314. [http://dx.doi.org/10.3390/jpm11121314] [PMID: 34945786] [http://dx.doi.org/10.3390/jpm11121314] [PMID: 34945786] [12] Kovina, M.V.; Krasheninnikov, M.E.; Dyuzheva, T.G. Human endometrial stem cells: High-yield isolation and characterization. Cytotherapy, 2018, 20(3), 361-374. [http://dx.doi.org/10.1016/j.jcyt.2017.12.012] [PMID: 29397307] [http://dx.doi.org/10.1016/j.jcyt.2017.12.012] [PMID: 29397307] [13] Wang, F.; Qualls, A.E.; Marques-Fernandez, L.; Colucci, F. Biology and pathology of the uterine microenvironment and its natural killer cells. Cell. Mol. Immunol., 2021, 18(9), 2101-2113. [http://dx.doi.org/10.1038/s41423-021-00739-z] [PMID: 34426671] [http://dx.doi.org/10.1038/s41423-021-00739-z] [PMID: 34426671] [14] Cousins, F.L.; Pandoy, R.; Jin, S.; Gargett, C.E. The elusive endometrial epithelial stem/progenitor cells. Front. Cell Dev. Biol., 2021, 9, 640319. [http://dx.doi.org/10.3389/fcell.2021.640319] [PMID: 33898428] [http://dx.doi.org/10.3389/fcell.2021.640319] [PMID: 33898428] [15] Liu, M.; Ji, M.; Cheng, J. Deciphering a critical role of uterine epithelial SHP2 in parturition initiation at single cell resolution. Nat. Commun., 2023, 14(1), 7356. [http://dx.doi.org/10.1038/s41467-023-43102-8] [PMID: 37963860] [http://dx.doi.org/10.1038/s41467-023-43102-8] [PMID: 37963860] [16] Arnold, J.T.; Kaufman, D.G.; Seppälä, M.; Lessey, B.A. Endometrial stromal cells regulate epithelial cell growth in vitro: a new co-culture model. Hum. Reprod., 2001, 16(5), 836-845. [http://dx.doi.org/10.1093/humrep/16.5.836] [PMID: 11331626] [http://dx.doi.org/10.1093/humrep/16.5.836] [PMID: 11331626] [17] Gargett, C.E. Uterine stem cells: What is the evidence? Hum. Reprod. Update, 2007, 13(1), 87-101. [http://dx.doi.org/10.1093/humupd/dml045] [PMID: 16960017] [http://dx.doi.org/10.1093/humupd/dml045] [PMID: 16960017] [18] Schutte, S.C.; Taylor, R.N. A tissue-engineered human endometrial stroma that responds to cues for secretory differentiation, decidualization, and menstruation. Fertil. Steril., 2012, 97(4), 997-1003. [http://dx.doi.org/10.1016/j.fertnstert.2012.01.098] [PMID: 22306710] [http://dx.doi.org/10.1016/j.fertnstert.2012.01.098] [PMID: 22306710] [19] Shved, N.; Egorova, A.; Osinovskaya, N.; Kiselev, A. Development of primary monolayer cell model and organotypic model of uterine leiomyoma. Methods Protoc., 2022, 5(1), 16. [http://dx.doi.org/10.3390/mps5010016] [PMID: 35200532] [http://dx.doi.org/10.3390/mps5010016] [PMID: 35200532] [20] Chitcholtan, K.; Asselin, E.; Parent, S.; Sykes, P.H.; Evans, J.J. Differences in growth properties of endometrial cancer in three dimensional (3D) culture and 2D cell monolayer. Exp. Cell Res., 2013, 319(1), 75-87. [http://dx.doi.org/10.1016/j.yexcr.2012.09.012] [PMID: 23022396] [http://dx.doi.org/10.1016/j.yexcr.2012.09.012] [PMID: 23022396] [21] Xu, J.; Zhang, L.; Ye, Z. A 3D “sandwich” co-culture system with vascular niche supports mouse embryo development from E3.5 to E7.5 in vitro. Stem Cell Res. Ther., 2023, 14(1), 349. [http://dx.doi.org/10.1186/s13287-023-03583-2] [PMID: 38072932] [http://dx.doi.org/10.1186/s13287-023-03583-2] [PMID: 38072932] [22] Cheng, Y.H.; Huang, C.W.; Lien, H.T. A preliminary investigation of the roles of endometrial cells in endometriosis development via in vitro and in vivo analyses. Int. J. Mol. Sci., 2024, 25(7), 3873. [http://dx.doi.org/10.3390/ijms25073873] [PMID: 38612685] [http://dx.doi.org/10.3390/ijms25073873] [PMID: 38612685] [23] Muruganandan, S.; Fan, X.; Dhal, S.; Nayak, N.R. Development of a 3D tissue slice culture model for the study of human endometrial repair and regeneration. Biomolecules, 2020, 10(1), 136. [http://dx.doi.org/10.3390/biom10010136] [PMID: 31947662] [http://dx.doi.org/10.3390/biom10010136] [PMID: 31947662] [24] Hellström, M.; El-Akouri, R.R.; Sihlbom, C. Towards the development of a bioengineered uterus: Comparison of different protocols for rat uterus decellularization. Acta Biomater., 2014, 10(12), 5034-5042. [http://dx.doi.org/10.1016/j.actbio.2014.08.018] [PMID: 25169258] [http://dx.doi.org/10.1016/j.actbio.2014.08.018] [PMID: 25169258] [25] Sehic, E.; de Miguel Gómez, L.; Rabe, H. Transplantation of a bioengineered tissue patch promotes uterine repair in the sheep. Biomater. Sci., 2024, 12(8), 2136-2148. [http://dx.doi.org/10.1039/D3BM01912H] [PMID: 38482883] [http://dx.doi.org/10.1039/D3BM01912H] [PMID: 38482883] [26] Daryabari, S.S.; Fendereski, K.; Ghorbani, F. Whole-organ decellularization of the human uterus and in vivo application of the bio-scaffolds in animal models. J. Assist. Reprod. Genet., 2022, 39(6), 1237-1247. [http://dx.doi.org/10.1007/s10815-022-02492-2] [PMID: 35513746] [http://dx.doi.org/10.1007/s10815-022-02492-2] [PMID: 35513746] [27] Wiwatpanit, T.; Murphy, A.R.; Lu, Z. Scaffold-free endometrial organoids respond to excess androgens associated with polycystic ovarian syndrome. J. Clin. Endocrinol. Metab., 2020, 105(3), 769-780. [http://dx.doi.org/10.1210/clinem/dgz100] [PMID: 31614364] [http://dx.doi.org/10.1210/clinem/dgz100] [PMID: 31614364] [28] Li, W-X.; Liang, G-T.; Yan, W. Artificial uterus on a microfluidic chip. Chin. J. Anal. Chem., 2013, 41(4), 467-472. [http://dx.doi.org/10.1016/S1872-2040(13)60639-8] [http://dx.doi.org/10.1016/S1872-2040(13)60639-8] [29] Xiao, S.; Coppeta, J.R.; Rogers, H.B. A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle. Nat. Commun., 2017, 8(1), 14584. [http://dx.doi.org/10.1038/ncomms14584] [PMID: 28350383] [http://dx.doi.org/10.1038/ncomms14584] [PMID: 28350383] [30] Young, R.E.; Huh, D.D. Organ-on-a-chip technology for the study of the female reproductive system. Adv. Drug Deliv. Rev., 2021, 173, 461-478. [http://dx.doi.org/10.1016/j.addr.2021.03.010] [PMID: 33831478] [http://dx.doi.org/10.1016/j.addr.2021.03.010] [PMID: 33831478] [31] Li, Y.; Tang, P.; Cai, S.; Peng, J.; Hua, G. Organoid based personalized medicine: from bench to bedside. Cell Regen. (Lond.), 2020, 9(1), 21. [http://dx.doi.org/10.1186/s13619-020-00059-z] [PMID: 33135109] [http://dx.doi.org/10.1186/s13619-020-00059-z] [PMID: 33135109] [32] Heidari-Khoei, H.; Esfandiari, F.; Hajari, M.A.; Ghorbaninejad, Z.; Piryaei, A.; Baharvand, H. Organoid technology in female reproductive biomedicine. Reprod. Biol. Endocrinol., 2020, 18(1), 64. [http://dx.doi.org/10.1186/s12958-020-00621-z] [PMID: 32552764] [http://dx.doi.org/10.1186/s12958-020-00621-z] [PMID: 32552764] [33] Arjmand, B.; Rabbani, Z.; Soveyzi, F. Advancement of organoid technology in regenerative medicine. Regen. Eng. Transl. Med., 2023, 9(1), 83-96. [http://dx.doi.org/10.1007/s40883-022-00271-0] [PMID: 35968268] [http://dx.doi.org/10.1007/s40883-022-00271-0] [PMID: 35968268] [34] Yang, S.; Hu, H.; Kung, H. Organoids: The current status and biomedical applications. MedComm, 2023, 4(3), e274. [http://dx.doi.org/10.1002/mco2.274] [PMID: 37215622] [http://dx.doi.org/10.1002/mco2.274] [PMID: 37215622] [35] Alzamil, L.; Nikolakopoulou, K.; Turco, M.Y. Organoid systems to study the human female reproductive tract and pregnancy. Cell Death Differ., 2021, 28(1), 35-51. [http://dx.doi.org/10.1038/s41418-020-0565-5] [PMID: 32494027] [http://dx.doi.org/10.1038/s41418-020-0565-5] [PMID: 32494027] [36] Rawlings, T.M.; Makwana, K.; Tryfonos, M.; Lucas, E.S. Organoids to model the endometrium: Implantation and beyond. Reprod. Fertility, 2021, 2(3), R85-R101. [http://dx.doi.org/10.1530/RAF-21-0023] [PMID: 35118399] [http://dx.doi.org/10.1530/RAF-21-0023] [PMID: 35118399] [37] Chumduri, C.; Turco, M.Y. Organoids of the female reproductive tract. J. Mol. Med. (Berl.), 2021, 99(4), 531-553. [http://dx.doi.org/10.1007/s00109-020-02028-0] [PMID: 33580825] [http://dx.doi.org/10.1007/s00109-020-02028-0] [PMID: 33580825] [38] Gu, Z.Y.; Jia, S.Z.; Liu, S.; Leng, J.H. Endometrial organoids: A new model for the research of endometrial-related diseases. Biol. Reprod., 2020, 103(5), 918-926. [http://dx.doi.org/10.1093/biolre/ioaa124] [PMID: 32697306] [http://dx.doi.org/10.1093/biolre/ioaa124] [PMID: 32697306] 37 1

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endometriosisinfertility

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

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