间充质基质细胞来源细胞外囊泡在妇产科学中的治疗潜力

近年来，间充质基质细胞（MSC）治疗作为医学领域的一个重要发展趋势受到广泛研究。然而，该疗法面临若干临床局限性，包括免疫反应、肿瘤风险以及归巢效率低等问题。因此，采用MSC来源细胞外囊泡（MSC-EV），特别是外泌体的无细胞策略，正作为一种日益受到认可的更安全替代方案而被研究。本小型综述旨在总结目前关于MSC-EV在女性生殖系统疾病中治疗潜力的临床前和早期临床证据，重点关注早发性卵巢功能不全和薄型子宫内膜，并概述其临床应用转化过程中面临的主要挑战。临床前和临床数据表明，MSC-EV通过转运微小RNA、蛋白质和脂质来改变靶组织功能。在化疗诱导的早发性卵巢功能不全模型中，MSC-EV可恢复卵泡发生，提高抗缪勒管激素水平，并减少颗粒细胞凋亡。在薄型子宫内膜模型中，囊泡通过无翅型相关整合位点/β-连环蛋白通路以及丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）通路改善组织再生并刺激血管生成。总体而言，MSC-EV可作为生殖医学中一种可行的无细胞治疗选择，但仍需要标准化方案和可靠的临床试验。

1. Cen J, Zhang Y, Bai Y, et al. Research progress of stem cell therapy for endometrial injury. Mater Today Bio. 2022;16:100389. doi: 10.1016/j.mtbio.2022.100389

2. Park H-S, Chugh RM, Seok J, et al. Comparison of the therapeutic effects between stem cells and exosomes in primary ovarian insufficiency: as promising as cells but different persistency and dosage. Stem Cell Res Ther. 2023;14(1):165. doi: 10.1186/s13287-023-03397-2

3. Zhang X, Wang S. Current status and future prospects of mesenchymal stem cell-derived exosomes therapy for premature ovarian insufficiency. J Ovarian Res. 2025;18(1):231. doi: 10.1186/s13048-025-01813-0

4. Elahi N, Ai J, Makoolati Z. A review on treatment of premature ovarian insufficiency: characteristics, limitations, and challenges of stem cell versus exosome therapy. Vet Med Int. 2023;2023(1):5760011. doi: 10.1155/2023/5760011

5. Duval C, Wyse BA, Tsang BK, Librach CL. Extracellular vesicles and their content in the context of polycystic ovarian syndrome and endometriosis: a review. J Ovarian Res. 2024;17(1):160. doi: 10.1186/s13048-024-01480-7

6. Yang Y, Rui B, Kim JH. Roles of exosomes in microenvironment-related premature ovarian insufficiency: mechanisms and therapeutic intervention. Reprod Biol Endocrinol. 2025;24(1):12. doi: 10.1186/s12958-025-01514-9

7. Xiao Y, Peng Y, Zhang C, Liu W, Wang K, Li J. hucMSC-derived exosomes protect ovarian reserve and restore ovarian function in cisplatin treated mice. J Biomed Res. 2023;37(5):382. doi: 10.7555/JBR.36.20220166

8. Hoang DH, Nguyen TD, Nguyen HP, et al. Differential wound healing capacity of mesenchymal stem cell-derived exosomes originated from bone marrow, adipose tissue and umbilical cord under serum- and xeno-free condition. Front Mol Biosci. 2020;7:119. doi: 10.3389/fmolb.2020.00119The Eurasian Journal of Life Sciences 2026; 2 (1) 75

9. Serhal N, Brassart B, Nannan L, et al. Angiogenic potential of small extracellular vesicles produced by stimulated mesenchymal stromal cells under hypoxic conditions. J Extracell Biol. 2026;5(1):e70105. doi: 10.1002/jex2.70105

10. Sultania A, Brahadeeswaran S, Kolasseri AE, Jayanthi S, Tamizhselvi R. Menopause mysteries: the exosome-inflammation connection. J Ovarian Res. 2025;18(1):12. doi: 10.1186/s13048-025-01591-9

11. Zhang H, Fang Y, Gao Y, et al. Brown adipose tissue-derived exosomes delay fertility decline in aging mice. Front Endocrinol. 2023;14:1180104. doi: 10.3389/fendo.2023.1180104

12. Ding K, Wang X, Liu W, et al. Engineering modification of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorates polycystic ovary syndrome by enhancing the ovarian environment and regulating follicular development. Stem Cell Res Ther. 2025;16(1):481. doi: 10.1186/s13287-025-04610-0

13. Lin J, Wang Z, Huang J, et al. Microenvironment-protected exosome-hydrogel for facilitating endometrial regeneration, fertility restoration, and live birth of offspring. Small. 2021;17(11):2007235. doi: 10.1002/smll.202007235

14. Hu J, Dong J, Zeng Z, et al. Using exosomal miRNAs extracted from porcine follicular fluid to investigate their role in oocyte development. BMC Vet Res. 2020;16(1):485. doi: 10.1186/s12917-020-02711-x

15. Ebrahimi M, Davari-Tanha F, Sahaiyan G, et al. A single-blind randomized controlled trial of intrauterine mesenchymal stem cell-derived exosome injection for improving IVF outcomes in infertile women with thin endometrium. Int J Womens Health Reprod Sci. 2025. doi: 10.15296/ijwhr.2025.9010.

16. Navarro C, Torrecillas Cabrera P, Teppa Garrán A. Comparative analysis of the use of autologous exosomes and platelet-derived growth factors in women with premature ovarian insufficiency and infertility: A prospective, randomized, observational, analytical study. Regen Ther. 2025;30:309–320. doi: 10.1016/j.reth.2025.06.007

17. Rezaei-Kiasari Z, Zamaniyan M, Khodashenas S, et al. The first case report of a pregnancy after exosome therapy in diminished ovarian reserve patient. Int J Clin Med Case Rep. 2024;5(6):1–4.

18. Geng Z, Guo H, Li Y, Liu Y, Zhao Y. Stem cell-derived extracellular vesicles: A novel and potential remedy for primary ovarian insufficiency. Front Cell Dev Biol. 2023;11:1090997. doi: 10.3389/fcell.2023.1090997

19. Moustaki M, Kontogeorgi A, Tsangkalova G, et al. Biological therapies for premature ovarian insufficiency: what is the evidence? Front Reprod Health. 2023;5:1194575. doi: 10.3389/frph.2023.1194575