ADVANCES IN ENDOMETRIOSIS THERAPY: A REVIEW OF TARGETED THERAPIES, NANOPARTICLES AND STEM CELLS
Abstract
Background: Endometriosis is an estrogen-dependent chronic inflammatory disease characterized by the presence of active endometrium outside the uterine cavity, most commonly in the pelvis. It affects an estimated 10-15% of women of childbearing age and is often associated with infertility, chronic pelvic pain, painful menstruation, and dyspareunia. Despite its high prevalence and significant impact on quality of life, the cause of endometriosis remains unclear, and the available treatment methods have many limitations.
Aim: This article aims to review current developments in endometriosis treatment, with a focus on new therapeutic strategies involving targeted therapies, nanoparticles and stem cells.
Methods: An analysis of the latest (2015-2025) literature from databases such as PubMed and Google Scholar was conducted to synthesize the available information. Search terms included combinations of “Endometriosis treatment,” “pathogenesis of Endometriosis,” “an update on Endometriosis,” “new therapeutics in Endometriosis,” and “immunotherapy in Endometriosis,” “stem cells and the Endometrium.”
Results: In recent years, there has been significant progress in developing targeted therapies that modulate specific signaling pathways, hormone receptors, inflammatory cytokines, and angiogenesis within endometrial lesions. Concurrently, the importance of nanotechnology in medicine, particularly in the context of precision drug delivery using nanoparticles, is growing. Additionally, regenerative therapies using stem cells are receiving increasing attention. These therapies offer the potential to repair damaged tissues and modulate the immune response.
Conclusion: Although preliminary studies are promising, the introduction of these innovative therapies requires further multi-center studies and evaluation of safety and cost. The integration of targeted therapies, nanotechnology and stem cells along with modern molecular diagnostics may soon revolutionize the treatment of endometriosis. This will pave the way for more effective and less invasive methods to improve patients' quality of life.
References
Zondervan, K. T., Becker, C. M., & Missmer, S. A. (2020). Endometriosis. The New England journal of medicine, 382(13), 1244–1256. https://doi.org/10.1056/NEJMra1810764
Troìa, L., & Luisi, S. (2021). An update on Endometriosis: what we know from lab to clinic. Minerva obstetrics and gynecology, 73(3), 273–274. https://doi.org/10.23736/S2724-606X.21.04824-7
Mariadas, H., Chen, J. H., & Chen, K. H. (2025). The Molecular and Cellular Mechanisms of Endometriosis: From Basic Pathophysiology to Clinical Implications. International journal of molecular sciences, 26(6), 2458. https://doi.org/10.3390/ijms26062458
Wang, P. H., Yang, S. T., Chang, W. H., Liu, C. H., Lee, F. K., & Lee, W. L. (2022). Endometriosis: Part I. Basic concept. Taiwanese journal of obstetrics & gynecology, 61(6), 927–934. https://doi.org/10.1016/j.tjog.2022.08.002
Shi, J., Tan, X., Feng, G., Zhuo, Y., Jiang, Z., Banda, S., Wang, L., Zheng, W., Chen, L., Yu, D., & Guo, C. (2023). Research advances in drug therapy of endometriosis. Frontiers in pharmacology, 14, 1199010. https://doi.org/10.3389/fphar.2023.1199010
Guo S. W. (2009). Recurrence of endometriosis and its control. Human reproduction update, 15(4), 441–461. https://doi.org/10.1093/humupd/dmp007
Barra, F., Laganà, A. S., Casarin, J., Ghezzi, F., Ferro Desideri, L., Scala, C., & Ferrero, S. (2019). Molecular Targets for Endometriosis Therapy: Where We Are and Where We Are Going?. International journal of fertility & sterility, 13(2), 89–92. https://doi.org/10.22074/ijfs.2019.5736
Slayden, O., Luo, F., Park, Y., Moses, A. S., Demessie, A. A., Singh, P., Korzun, T., Taratula, O., & Taratula, O. (2024). Targeted nanoparticles for imaging and therapy of endometriosis†. Biology of reproduction, 110(6), 1191–1200. https://doi.org/10.1093/biolre/ioae073
Taylor, H. S., Giudice, L. C., Lessey, B. A., Abrao, M. S., Kotarski, J., Archer, D. F., Diamond, M. P., Surrey, E., Johnson, N. P., Watts, N. B., Gallagher, J. C., Simon, J. A., Carr, B. R., Dmowski, W. P., Leyland, N., Rowan, J. P., Duan, W. R., Ng, J., Schwefel, B., Thomas, J. W., … Chwalisz, K. (2017). Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist. The New England journal of medicine, 377(1), 28–40. https://doi.org/10.1056/NEJMoa1700089
Surrey, E., Taylor, H. S., Giudice, L., Lessey, B. A., Abrao, M. S., Archer, D. F., Diamond, M. P., Johnson, N. P., Watts, N. B., Gallagher, J. C., Simon, J. A., Carr, B. R., Dmowski, W. P., Leyland, N., Singh, S. S., Rechberger, T., Agarwal, S. K., Duan, W. R., Schwefel, B., Thomas, J. W., … Chwalisz, K. (2018). Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies. Obstetrics and gynecology, 132(1), 147–160. https://doi.org/10.1097/AOG.0000000000002675
Kapoor, R., Stratopoulou, C. A., & Dolmans, M. M. (2021). Pathogenesis of Endometriosis: New Insights into Prospective Therapies. International journal of molecular sciences, 22(21), 11700. https://doi.org/10.3390/ijms222111700
Brichant, G., Laraki, I., Henry, L., Munaut, C., & Nisolle, M. (2021). New Therapeutics in Endometriosis: A Review of Hormonal, Non-Hormonal, and Non-Coding RNA Treatments. International journal of molecular sciences, 22(19), 10498. https://doi.org/10.3390/ijms221910498
Dolmans, M. M., & Donnez, J. (2022). Emerging Drug Targets for Endometriosis. Biomolecules, 12(11), 1654. https://doi.org/10.3390/biom12111654
Zhou, C., Feng, M., Chen, Y., Lv, S., Zhang, Y., Chen, J., Zhang, R., & Huang, X. (2023). Unraveling immunotherapeutic targets for endometriosis: a transcriptomic and single-cell analysis. Frontiers in immunology, 14, 1288263. https://doi.org/10.3389/fimmu.2023.1288263
Lulseged, B. A., Ramaiyer, M. S., Michel, R., Saad, E. E., Ozpolat, B., & Borahay, M. A. (2024). The Role of Nanomedicine in Benign Gynecologic Disorders. Molecules (Basel, Switzerland), 29(9), 2095. https://doi.org/10.3390/molecules29092095
Friend D. R. (2017). Drug delivery for the treatment of endometriosis and uterine fibroids. Drug delivery and translational research, 7(6), 829–839. https://doi.org/10.1007/s13346-017-0423-2
Zhu, S., Zhang, J., Xue, N., Zhu, X., Li, F., Dai, Q., Qing, X., Chen, D., Liu, X., Wei, Z., & Cao, Y. (2023). Highly specific neutrophil-mediated delivery of albumin nanoparticles to ectopic lesion for endometriosis therapy. Journal of nanobiotechnology, 21(1), 81. https://doi.org/10.1186/s12951-023-01831-4
Kiisholts, K., Kurrikoff, K., Arukuusk, P., Porosk, L., Peters, M., Salumets, A., & Langel, Ü. (2021). Cell-Penetrating Peptide and siRNA-Mediated Therapeutic Effects on Endometriosis and Cancer In Vitro Models. Pharmaceutics, 13(10), 1618. https://doi.org/10.3390/pharmaceutics13101618
Wu, Y., Sun, J., Li, A., & Chen, D. (2018). The promoted delivery of RRM2 siRNA to vascular smooth muscle cells through liposome-polycation-DNA complex conjugated with cell penetrating peptides. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 103, 982–988. https://doi.org/10.1016/j.biopha.2018.03.068
Liu, J., Liu, Q., & Chen, X. (2020). The Immunomodulatory Effects of Mesenchymal Stem Cells on Regulatory B Cells. Frontiers in immunology, 11, 1843. https://doi.org/10.3389/fimmu.2020.01843
Varela-Pombo, C., López-Viñas, B., Tustain, S. Q., Maquieira, C. G., Mateos, J., Fafián-Labora, J., & Arufe, M. C. (2025). Therapeutic application of mesenchymal stem cells in endometriosis. Life sciences, 379, 123851. Advance online publication. https://doi.org/10.1016/j.lfs.2025.123851
Chen, W., Huang, Y., Han, J., Yu, L., Li, Y., Lu, Z., Li, H., Liu, Z., Shi, C., Duan, F., & Xiao, Y. (2016). Immunomodulatory effects of mesenchymal stromal cells-derived exosome. Immunologic research, 64(4), 831–840. https://doi.org/10.1007/s12026-016-8798-6
Cevik, E. C., Mamillapalli, R., & Taylor, H. S. (2025). Stem cells and female reproduction: endometrial physiology, disease and therapy. Stem cells (Dayton, Ohio), 43(5), sxaf016. https://doi.org/10.1093/stmcls/sxaf016
Chatzianagnosti, S., Dermitzakis, I., Theotokis, P., Kousta, E., Mastorakos, G., & Manthou, M. E. (2024). Application of Mesenchymal Stem Cells in Female Infertility Treatment: Protocols and Preliminary Results. Life (Basel, Switzerland), 14(9), 1161. https://doi.org/10.3390/life14091161
Kong, Y., Shao, Y., Ren, C., & Yang, G. (2021). Endometrial stem/progenitor cells and their roles in immunity, clinical application, and endometriosis. Stem cell research & therapy, 12(1), 474. https://doi.org/10.1186/s13287-021-02526-z
Varela-Pombo, C., López-Viñas, B., Tustain, S. Q., Maquieira, C. G., Mateos, J., Fafián-Labora, J., & Arufe, M. C. (2025). Therapeutic application of mesenchymal stem cells in endometriosis. Life sciences, 379, 123851. Advance online publication. https://doi.org/10.1016/j.lfs.2025.123851
Atiya, H. I., Frisbie, L., Goldfeld, E., Orellana, T., Donnellan, N., Modugno, F., Calderon, M., Watkins, S., Zhang, R., Elishaev, E., Soong, T. R., Vlad, A., & Coffman, L. (2022). Endometriosis-Associated Mesenchymal Stem Cells Support Ovarian Clear Cell Carcinoma through Iron Regulation. Cancer research, 82(24), 4680–4693. https://doi.org/10.1158/0008-5472.CAN-22-1294
Esfandyari, S., Chugh, R. M., Park, H. S., Hobeika, E., Ulin, M., & Al-Hendy, A. (2020). Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility. Cells, 9(10), 2253. https://doi.org/10.3390/cells9102253
de Miguel-Gómez, L., López-Martínez, S., Francés-Herrero, E., Rodríguez-Eguren, A., Pellicer, A., & Cervelló, I. (2021). Stem Cells and the Endometrium: From the Discovery of Adult Stem Cells to Pre-Clinical Models. Cells, 10(3), 595. https://doi.org/10.3390/cells10030595
Cousins, F. L., McKinnon, B. D., Mortlock, S., Fitzgerald, H. C., Zhang, C., Montgomery, G. W., & Gargett, C. E. (2023). New concepts on the etiology of endometriosis. The journal of obstetrics and gynaecology research, 49(4), 1090–1105. https://doi.org/10.1111/jog.15549
Cheng, Y., Guo, Q., Cheng, Y., Wang, D., Sun, L., Liang, T., Wang, J., Wu, H., Peng, Z., & Zhang, G. (2025). Endostatin-expressing endometrial mesenchymal stem cells inhibit angiogenesis in endometriosis through the miRNA-21-5p/TIMP3/PI3K/Akt/mTOR pathway. Stem cells translational medicine, 14(2), szae079. https://doi.org/10.1093/stcltm/szae079
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Copyright (c) 2025 Magdalena Koss, Weronika Ziomek, Elżbieta Bebrysz, Jan Palmi, Karolina Dębek-Kalinowska, Piotr Bartnik, Jarosław Baran, Ida Dunder, Mateusz Biszewski, Aleksandra Drabik

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