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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Kazan medical journal</journal-id><journal-title-group><journal-title xml:lang="en">Kazan medical journal</journal-title><trans-title-group xml:lang="ru"><trans-title>Казанский медицинский журнал</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0368-4814</issn><issn publication-format="electronic">2587-9359</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">693214</article-id><article-id pub-id-type="doi">10.17816/KMJ693214</article-id><article-id pub-id-type="edn">PYXOHK</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Reviews</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Обзоры</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Effects of autophagy modulators on the therapeutic efficacy of multipotent mesenchymal stromal cells</article-title><trans-title-group xml:lang="ru"><trans-title>Влияние модуляторов аутофагии на терапевтическую эффективность мультипотентных мезенхимальных стромальных клеток</trans-title></trans-title-group><trans-title-group xml:lang="zh"><trans-title>自噬调节剂对多潜能间充质基质细胞治疗效果的影响</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7475-9517</contrib-id><contrib-id contrib-id-type="spin">2915-7500</contrib-id><name-alternatives><name xml:lang="en"><surname>Ivanov</surname><given-names>Vladislav A.</given-names></name><name xml:lang="ru"><surname>Иванов</surname><given-names>Владислав Александрович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Postgraduate student, Depart. of Pathological Physiology</p></bio><bio xml:lang="ru"><p>аспирант, каф. патологической физиологии</p></bio><email>vlanov123@yandex.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5698-8404</contrib-id><contrib-id contrib-id-type="spin">5761-9324</contrib-id><name-alternatives><name xml:lang="en"><surname>Grebnev</surname><given-names>Dmitry Y.</given-names></name><name xml:lang="ru"><surname>Гребнев</surname><given-names>Дмитрий Юрьевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Dr. Sci. (Medicine), Assistant Professor, Head, Depart. of Pathological Physiology</p></bio><bio xml:lang="ru"><p>д-р мед. наук, доцент, заведующий, каф. патологической физиологии</p></bio><email>dr-grebnev77@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6895-7947</contrib-id><contrib-id contrib-id-type="spin">7335-7294</contrib-id><name-alternatives><name xml:lang="en"><surname>Maklakova</surname><given-names>Irina Y.</given-names></name><name xml:lang="ru"><surname>Маклакова</surname><given-names>Ирина Юрьевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Dr. Sci. (Medicine), Assistant Professor, Head, Depart. of Normal Physiology</p></bio><bio xml:lang="ru"><p>д-р мед. наук, доцент, заведующая, каф. нормальной физиологии</p></bio><email>makliu@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Ural state medical university</institution></aff><aff><institution xml:lang="ru">Уральский государственный медицинский университет</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Sverdlovsk Regional Clinical Neuropsychiatric Hospital for War Veterans</institution></aff><aff><institution xml:lang="ru">Свердловский областной клинический психоневрологический госпиталь для ветеранов войн</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2026-03-06" publication-format="electronic"><day>06</day><month>03</month><year>2026</year></pub-date><pub-date date-type="pub" iso-8601-date="2026-04-07" publication-format="electronic"><day>07</day><month>04</month><year>2026</year></pub-date><volume>107</volume><issue>2</issue><issue-title xml:lang="en">Kazan medical journal</issue-title><issue-title xml:lang="ru">Казанский медицинский журнал</issue-title><fpage>220</fpage><lpage>230</lpage><history><date date-type="received" iso-8601-date="2025-10-15"><day>15</day><month>10</month><year>2025</year></date><date date-type="accepted" iso-8601-date="2025-12-25"><day>25</day><month>12</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2026, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2026, Эко-Вектор</copyright-statement><copyright-statement xml:lang="zh">Copyright ©; 2026,</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/" start_date="2029-04-07"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc-nd/4.0/</ali:license_ref></license></permissions><self-uri xlink:href="https://kazanmedjournal.ru/kazanmedj/article/view/693214">https://kazanmedjournal.ru/kazanmedj/article/view/693214</self-uri><abstract xml:lang="en"><p>Restoring damaged tissues and organs, particularly in cases of acute radiation injury, remains one of the major challenges in regenerative medicine. Acute radiation syndrome caused by high-dose ionizing radiation exposure is associated with profound suppression of hematopoiesis and damage to the bone marrow stroma. Multipotent mesenchymal stromal cells are regarded as a promising therapeutic tool because of their differentiation potential, immunomodulatory properties, secretion of trophic factors, and ability to support the hematopoietic niche. However, their clinical efficacy is limited by low survival under conditions of oxidative stress and inflammation. Mechanisms that increase the resistance of multipotent mesenchymal stromal cells to damaging factors and enhance their regenerative potential remain insufficiently studied.</p> <p>This work reviews current data on the role of autophagy—an evolutionarily conserved process of intracellular renewal—as a potential approach to increasing the functional activity of multipotent mesenchymal stromal cells.</p> <p>Pharmacologic strategies for autophagy modulation are discussed, including mTOR-dependent (sirolimus) and mTOR-independent (lithium, trehalose) approaches, as well as their effects on the survival, migration, and secretory activity of multipotent mesenchymal stromal cells. Particular attention is given to cell preconditioning as a strategy to enhance therapeutic efficacy in radiation injury.</p> <p>Available evidence supports the use of targeted autophagy activation as a key component in the development of standardized next-generation cell-based products capable of not only supporting but also actively restoring hematopoiesis after acute radiation exposure.</p></abstract><trans-abstract xml:lang="ru"><p>В настоящее время восстановление повреждённых тканей и органов, особенно при острых радиационных поражениях, остаётся одной из центральных задач регенеративной медицины. Острая лучевая болезнь, развивающаяся вследствие массивного воздействия ионизирующего излучения, сопровождается тяжёлым угнетением гемопоэза и повреждением стромы костного мозга. Несмотря на то что мультипотентные мезенхимальные стромальные клетки рассматриваются в качестве перспективного терапевтического инструмента благодаря способности к дифференцировке, иммуномодуляции, секреции трофических факторов и формированию гемопоэтической ниши, их клиническая эффективность ограничена низкой выживаемостью в условиях оксидативного стресса и воспаления. В то же время механизмы, способные повысить устойчивость мультипотентных мезенхимальных стромальных клеток к повреждающим факторам и усилить их регенераторный потенциал, остаются недостаточно изученными.</p> <p>В статье представлен анализ современных данных о роли аутофагии — эволюционно консервативного процесса внутриклеточного обновления, рассматриваемого как один из потенциальных способов повышения функциональной активности мультипотентных мезенхимальных стромальных клеток.</p> <p>Рассмотрены фармакологические стратегии модуляции аутофагии, включая mTOR-зависимые (сиролимус) и mTOR-независимые (литий, трегалоза) подходы, а также их влияние на выживаемость, миграцию и секреторную активность мультипотентных мезенхимальных стромальных клеток. Особое внимание уделено концепции прекондиционирования клеток как способа повышения их терапевтической эффективности при радиационных поражениях.</p> <p>Полученные данные позволяют рассматривать целенаправленную активацию аутофагии как ключевой элемент разработки стандартизированных клеточных препаратов нового поколения, способных не только поддерживать, но и активно восстанавливать гемопоэз после острого лучевого воздействия.</p></trans-abstract><trans-abstract xml:lang="zh"><p>目前，受损组织与器官的修复，特别是在急性放射损伤条件下，仍是再生医学领域的核心难题之一。急性放射病是由大剂量电离辐射引起的，伴随着造血功能严重抑制和骨髓基质损伤。多潜能间充质基质细胞（MSCs）因其具有多向分化潜能、免疫调节功能、分泌营养因子以及构建造血微环境的能力，被视为极具潜力的治疗工具。然而，由于 MSCs 在氧化应激和炎症微环境中的存活率较低，其临床应用效果受到显著限制。目前，关于如何增强 MSCs 对损伤因素的抵抗力并提高其再生潜能的机制尚未得到充分阐明。</p> <p>本文综述了自噬在多潜能间充质基质细胞功能调节中的作用。自噬作为一种进化保守的细胞内更新过程，被视为提升 MSCs 功能活性的潜在重要手段。文章重点分析了多种自噬调节策略，包括 mTOR 依赖性途径（如西罗莫司作用）及 mTOR 非依赖性途径（如锂盐、海藻糖作用），并探讨了这些策略对 MSCs 存活率、迁移能力及分泌功能的影响。此外，本文深入剖析了细胞预处理作为一种在放射损伤中增强细胞治疗效果的关键策略。现有研究表明，靶向激活自噬可作为研发新一代标准化细胞制剂的关键环节，使其不仅能维持造血功能，还能在急性放射损伤后促进造血系统的有效重建。</p></trans-abstract><kwd-group xml:lang="en"><kwd>multipotent mesenchymal stromal cells</kwd><kwd>autophagy</kwd><kwd>oxidative stress</kwd><kwd>radiation injury</kwd><kwd>cell therapy</kwd><kwd>review</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>мультипотентные мезенхимальные стромальные клетки</kwd><kwd>аутофагия</kwd><kwd>оксидативный стресс</kwd><kwd>радиационное повреждение</kwd><kwd>клеточная терапия</kwd><kwd>обзор</kwd></kwd-group><kwd-group xml:lang="zh"><kwd>多潜能间充质基质细胞</kwd><kwd>自噬</kwd><kwd>氧化应激</kwd><kwd>放射损伤</kwd><kwd>细胞治疗</kwd><kwd>综述</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Yu P, Liu B, Dong C, Chang Y. 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