Mesenchymal stromal cells-derived exosomes as a new approach to restoring endometrial functionality in reproductive medicine

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Abstract

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.

About the authors

Andrey D. Khegai

Lomonosov Moscow State University

Author for correspondence.
Email: kheg2022@gmail.com
ORCID iD: 0009-0004-2012-8092

4th year student, Faculty of Fundamental Medicine

Russian Federation, Moscow

Natalya P. Makarova

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: np_makarova@oparina4.ru
ORCID iD: 0000-0003-1396-7272

Dr. Bio. Sci., Leading Researcher at the Prof. B.V. Leonov Department of Assistive Technologies in Infertility Treatment

Russian Federation, Moscow

Alexander A. Kalugin

N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

Email: alex.kalugin2013@gmail.com

5th year student

Russian Federation, Moscow

Elena A. Kalinina

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: e_kalinina@oparina4.ru
ORCID iD: 0000-0002-8922-2878

Dr. Med. Sci., Professor, Head of the Prof. B.V. Leonov Department of Assistive Technologies in Infertility Treatment

Russian Federation, Moscow

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