biopreparatБИОпрепараты. Профилактика, диагностика, лечениеBiological Products. Prevention, Diagnosis, Treatment2221-996X2619-1156Scientific Centre for Expert Evaluation of Medicinal Products10.30895/2221-996X-2025-25-3-343-356biopreparat-735Research ArticleКЛЕТОЧНАЯ И ЭКЗОСОМАЛЬНАЯ ТЕРАПИЯCELL- AND EXOSOME-BASED THERAPIESЭкзосомы, продуцируемые мезенхимальными стромальными клетками, для терапии острого респираторного дистресс-синдрома: обзор доклинических и клинических исследованийMesenchymal stromal cell-derived exosomes for acute respiratory distress syndrome treatment: A review of preclinical and clinical trialshttps://orcid.org/0000-0003-2935-1325КуралесоваА. И.KuralesovaA. I.

Куралесова Альбина Ивановна, д-р биол. наук 

ул. Гамалеи, д. 18, Москва, 123098

Albina I. Kuralesova, Dr. Sci. (Biol.) 

18 Gamaleya St., Moscow 123098

https://orcid.org/0000-0002-0951-5380ГрошеваА. Г.GroshevaA. G.

Грошева Алла Германовна, канд. биол. наук

ул. Гамалеи, д. 18, Москва, 123098

Alla G. Grosheva, Cand. Sci. (Biol.) 

18 Gamaleya St., Moscow 123098

https://orcid.org/0000-0002-7594-0473ГенкинаЕ. Н.GenkinaE. N.

Генкина Елена Николаевна

ул. Гамалеи, д. 18, Москва, 123098

Elena N. Genkina

18 Gamaleya St., Moscow 123098

https://orcid.org/0000-0002-2063-2449ЕсмагамбетовИ. Б.EsmagambetovI. B.

Есмагамбетов Ильяс Булатович, канд. биол. наук 

ул. Гамалеи, д. 18, Москва, 123098

Ilias B. Esmagambetov, Cand. Sci. (Biol.) 

18 Gamaleya St., Moscow 123098

esmagambetov@gamaleya.orgФедеральное государственное бюджетное учреждение «Национальный исследовательский центр эпидемиологии и микробиологии имени почетного академика Н.Ф. Гамалеи» Министерства здравоохранения Российской ФедерацииРоссияNational Research Center for Epidemiology and Microbiology named after the honorary academician N.F. GamaleyaRussian Federation202529092025253343356Copyright © Куралесова А.И., Грошева А.Г., Генкина Е.Н., Есмагамбетов И.Б., 20252025Куралесова А.И., Грошева А.Г., Генкина Е.Н., Есмагамбетов И.Б.Kuralesova A.I., Grosheva A.G., Genkina E.N., Esmagambetov I.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.biopreparations.ru/jour/article/view/735ВВЕДЕНИЕ

ВВЕДЕНИЕ. В период пандемии COVID-19 диагноз острый респираторный дистресссиндром (ОРДС) констатировали у 15–33% пациентов, госпитализированных с заболеваниями легких. Вследствие возросших показателей больничной летальности и недостаточной эффективности существовавших на тот момент лекарственных средств возникла необходимость применения терапии мезенхимальными стромальными клетками (МСК). Содержащиеся в секретоме МСК экзосомы обладают регенеративной активностью, как и МСК, причем введение последних может быть сопряжено с риском тромбообразования. Обнадеживающие результаты доклинических испытаний препаратов на основе экзосом обусловливают  их  клиническое  применение.  Анализ  актуальных  данных  по  безопасности и эффективности инновационных препаратов на основе экзосом позволит выработать протоколы получения, хранения, транспортировки, а также оптимальные схемы применения препаратов для бесклеточной терапии ОРДС и других заболеваний легких.

ЦЕЛЬ

ЦЕЛЬ.   Анализ   результатов   доклинических   и   клинических   исследований   безопасности и эффективности препаратов на основе экзосом, продуцируемых МСК и предназначенных для бесклеточной терапии ОРДС и других заболеваний легких в качестве альтернативы медикаментозному лечению.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. Экзосомы, важнейший компонент секретомов различных клеток, осуществляют горизонтальный перенос генетической информации и биологически активных молекул. В доклинических испытаниях установлено, что полученные из секретома МСК экзосомы обладают выраженными регенеративными свойствами, схожими с МСК, и имеют ряд преимуществ: малые размеры, исключающие тромбообразование в легочных капиллярах; проникновение через гематоэнцефалический барьер; отсутствие тератогенности; обеспечение обмена эпигеномной информацией при межклеточных взаимодействиях. Введение препаратов на основе экзосом способствует регенерации поврежденной легочной ткани при ОРДС и других заболеваниях легких. Клинические исследования подтвердили безопасность и эффективность препаратов при ингаляционном,   внутривенном или сочетанном введении. Эффективность препаратов может быть повышена при совместном применении экзосом c МСК или при использовании экзосом, обогащенных гликопротеином СD24 (ключевая молекула врожденного иммунитета). Препараты на основе экзосом купируют ОРДС и другие заболевания легких благодаря своей регенеративной и иммуномодулирующей активности, а также способности снижать уровень «цитокинового шторма» и апоптоза и рассматриваются как перспективная бесклеточная (cells free) терапевтическая стратегия в лечении ОРДС.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. Проведенный анализ данных доклинических и  клинических  исследований свидетельствует о  высокой  эффективности  терапевтического  действия  препаратов на основе экзосом, однако целесообразны дальнейшие исследования безопасности препаратов и определения оптимальных схем лечения ОРДС.

INTRODUCTION

INTRODUCTION. During the COVID-19 pandemic, acute respiratory distress syndrome (ARDS) was diagnosed in 15–33% of patients hospitalised for pulmonary diseases. Hospital mortality rates increased. The existing medicinal products lacked effectiveness. Thus unconventional treatment methods were needed, such as mesenchymal stromal cell (MSC) therapy. The risk of blood clotting in the lung vessels after MSC injection made exosomes from MSC secretome a therapy of choice. Exosomes cross the blood-brain barrier and have regenerative effect similar to that of MSC. The promising results of preclinical trials for exosome-based drugs have stimulated their clinical use. Analysing their safety and effectiveness will allow us to develop protocols for their production, storage, and transportation, as well as optimal dose regimens for cell-free therapy of ARDS and other pulmonary diseases.

AIM

AIM. This study aimed to analyse performed preclinical and clinical studies on safety  and efficacy of MSC-derived exosome drugs intended for cell-free ARDS therapy and other pulmonary diseases as an alternative to drug therapy.

DISCUSSION

DISCUSSION. Exosomes, the most important secretome element in various cells, carry out horizontal transfer of genetic information and bioactive molecules. Animal models show that exosomes obtained from MSC secretome have regenerative abilities similar to MSC and offer various advantages: small size excluding blood clotting in the pulmonary capillaries; ability to penetrate blood-brain barrier, non-teratogenicity, and exchange of epigenomic information in cell-cell interactions. Preclinical in vivo studies have shown that exosomes affect regeneration of damaged lung tissue in ARDS and other lung diseases. Clinical trials have confirmed safety and effectiveness of inhalation, intravenous or combined administration. Drug effectiveness can be increased by combining exosomes with MSC or enriching them with CD24 (key molecule of innate immunity). Due to regenerative, immunomodulatory properties of exosomes, their ability to reduce the level of cytokine storm and apoptosis, they are used to treat ARDS and other lung diseases. Exosome preparations reverse ARDS and other diseases due to their regenerative and immunomodulatory effect, and ability to reduce cytokine storm and apoptosis. Thus exosomes are recognised as a new effective cell-free therapy.

CONCLUSIONS

CONCLUSIONS. Therapeutic effect of exosome-based preparations was analysed in experimental, preclinical, and clinical trials; however, further trials are required to determine ARDS safety and optimal treatment regimens.

ОРДСострый респираторный дистресс-синдромМСКмезенхимальные стромальные клеткиэкзосомыэкзосомальная терапиявезикулыдоклинические исследованияклинические исследованиярегенерацияврожденный иммунитетCOVID-19секретомARDSacute respiratory distress syndromeMSCsmesenchymal stem cellsexosomesexosomal therapyvesiclespreclinical trialsclinical trialsregenerationinnate immunityCOVID-19secretomeРабота выполнена в рамках государственного задания ФГБУ «НИЦЭМ им. Н.Ф. Гамалеи» Минздрава России «Разработка технологической платформы на основе экзосом, продуцируемых костно-мозговыми мезенхимальными стволовыми клетками человека, для создания средств терапии острого респираторного дистресс-синдрома», регистрационный номер 1023022100011-3The study was carried out as a part of the State Assignment of the Federal State Budgetary Institution National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. 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The authors declare that there are no conflicts of interest present.