Mesenchymal stromal cells-derived exosomes as a new approach to restoring endometrial functionality in reproductive medicine
Khegai A.D., Makarova N.P., Kalugin A.A., Kalinina E.A.
The endometrium is the mucous membrane of the uterine cavity, which undergoes cyclic processes of destruction and regeneration. The impairment of these processes can lead to infertility and various gynecological problems. In recent years, mesenchymal stromal cells-derived extracellular vesicles (MSC-EVs) have been considered as a promising tool for endometrial regenerative therapy. Extracellular vesicles contain biologically active molecules (microRNAs, proteins, growth factors) that stimulate endometrial repair mechanisms.
Preclinical studies in animal models demonstrate that intrauterine injection of MSC-EVs restores the morphology of the endometrium, increases the thickness of the mucous membrane, the number of endometrial glands, and reduces the number of collagen deposits. The first clinical studies confirm the safety and effectiveness of MSC-EVs in women with damaged endometrium, and also show their potential use in assisted reproductive technologies (ART) to prepare the endometrium for implantation and the birth of healthy children.
Conclusion: Despite the promising results, there are still some issues regarding the standardization of methods for MSC-EVs obtaining, the duration of their effect, dosage, and their long-term effectiveness. For the clinical use of MSC-EVs, the most optimal method of their isolation is a combination of tangential ultrafiltration and size exclusion chromatography. This method ensures high purity of the product in case of maintaining biological activity and its large-scale production. Further clinical trials with large samples are needed to optimize protocols and introduce this therapy into ART practice.
Authors’ contributions: Khegai A.D. – data collection and processing, writing the text of the article; Makarova N.P. – editing, approval of the final version of the article; Kalugin A.A. – data collection and processing; Kalinina E.A. – article editing.
Conflicts of interest: Authors declare lack of the possible conflicts of interest.
Funding: The study was carried out within the initiative scientific project “Study of the influence of extracellular vesicles derived from biological fluids of the reproductive organs and tissues on gametes, the process of fertilization and early human embryogenesis and implantation” (2025–2027, supervised by N.P. Makarova), Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
For citation: Khegai A.D., Makarova N.P., Kalugin A.A., Kalinina E.A. Mesenchymal stromal cells-derived exosomes as a new approach to restoring endometrial functionality in reproductive medicine.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (12): 38-43 (in Russian)
https://dx.doi.org/10.18565/aig.2025.342
Keywords
endometrium
infertility
extracellular vesicles
mesenchymal stromal cells
animal models
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Received 28.11.2025
Accepted 16.12.2025
About the Authors
Andrey D. Khegai, 4th year student, Lomonosov Moscow State University, 119234, Russia, Moscow, Leninsky Gory, 1, build. 12, kheg2022@gmail.com,https://orcid.org/0009-0004-2012-8092
Natalya P. Makarova, Dr. Bio. Sci., Leading Researcher at the Prof. B.V. Leonov Department of Assistive Technologies in Infertility Treatment, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4,
np_makarova@oparina4.ru, https://orcid.org/0000-0003-1396-7272
Alexander A. Kalugin, 5th year student, Pirogov Russian National Research Medical University, Ministry of Health of Russia, 117997, Russia, Moscow, Ostrovityanov str., 1, build. 7, alex.kalugin2013@gmail.com
Elena A. Kalinina, Dr. Med. Sci., Professor, Head of the Prof. B.V. Leonov Department of Assistive Technologies in Infertility Treatment, Academician V.I. Kulakov
National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4,
e_kalinina@oparina4.ru, https://orcid.org/0000-0002-8922-2878
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