vtioВестник трансплантологии и искусственных органовRussian Journal of Transplantology and Artificial Organs1995-1191Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation10.15825/1995-1191-2024-2-126-134vtio-1687Research ArticleРегенеративная медицина и клеточные технологииRegenerative Medicine and Cell TechnologiesВлияние путей и доз введения мультипотентных мезенхимальных стволовых клеток на эффективность клеточной терапииEffect of the delivery route and dose of multipotent mesenchymal stem cells on the efficacy of cell therapy (review)ПакН. В.PakN. V.

Пак Наталья Викторовна

194044, Санкт-Петербург, ул. Академика Лебедева, д. 6.

Тел. (812) 292-32-63

Natalya Pak

6, Akademika Lebedeva str., St. Petersburg, 194044

Phone: (812) 292-32-63

natalya_pak@mail.ruМурзинаЕ. В.MurzinaE. V.

Санкт-Петербург

 

St. Petersburg

elenmurzina@mail.ruАксеноваН. В.AksenovaN. V.

Санкт-Петербург

St. Petersburg

nataaks@mail.ruКрыловаТ. Г.KrylovaT. G.

Санкт-Петербург

St. Petersburg

niurakr@yandex.ruАлександровВ. Н.AleksandrovV. N.

Санкт-Петербург

St. Petersburg

vnaleks@yandex.ruФГБВОУ ВО «Военно-медицинская академия имени С.М. Кирова» Министерства обороны Российской ФедерацииРоссияKirov Military Medical AcademyRussian Federation202431012024262126134Copyright © Пак Н.В., Мурзина Е.В., Аксенова Н.В., Крылова Т.Г., Александров В.Н., 20242024Пак Н.В., Мурзина Е.В., Аксенова Н.В., Крылова Т.Г., Александров В.Н.Pak N.V., Murzina E.V., Aksenova N.V., Krylova T.G., Aleksandrov V.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.transpl.ru/vtio/article/view/1687

Терапевтический потенциал мультипотентных мезенхимальных стволовых клеток (ММСК) признан неоспоримым: помимо способности дифференцироваться в различные типы клеток и тем самым участвовать в восстановлении поврежденных тканей и органов они обладают способностью влиять на процессы регенерации посредством секреции паракринных факторов. То есть терапия посредством ММСК представляет собой особый вид медицинского вмешательства, который обладает как системным диапазоном терапевтической эффективности, так и локальной активностью на отдельных участках органов. В течение последних десятилетий терапия ММСК постоянно находится в процессе осторожного перехода от исследовательских разработок к клинически одобренным методам лечения. Согласно данным клинических испытаний, она редко демонстрирует серьезные нежелательные явления, хорошо переносится и достаточно безопасна в краткосрочном диапазоне, однако вместе с тем она имеет ряд ограничений по применению, в основном вследствие риска злокачественной трансформации. Успешность трансплантации стволовых клеток при лечении различных заболеваний подтверждена как в доклинических исследованиях, так и в клинической практике. Главными вопросами, возникающими при оценке терапевтической эффективности клеточной терапии посредством ММСК, являются тип клеток (адипогенные, костномозговые и т. д.), способ их введения, количество вводимых клеток, оптимальное количество инъекций. Появляется все больше экспериментальных и клинических данных, свидетельствующих о том, что как адекватный путь введения, так и адекватная доза могут повысить вероятность успеха терапии с использованием ММСК. Каждый путь введения клеток сопряжен с определенными издержками и преимуществами. Однако в целом данные о сравнительной эффективности различных путей введения клеток достаточно противоречивы. Вопрос оптимальной дозы трансплантируемых клеток также дебатируется, поскольку высокие дозы ММСК могут повышать риски осложнений и не оказывать должного эффекта как при системном, так и при локальном введении. Эти аспекты требуют дополнительной систематизации имеющихся данных для достижения максимального эффекта применения клеточной терапии путем выбора наиболее безопасных и целесообразных подходов.

Multipotent mesenchymal stem cells (MMSCs) are known to be excellent therapeutic agents. Apart from their ability to differentiate into various cell types, and thus participate in the repair of injured tissues and organs, they can influence the regeneration process through secretion of paracrine factors. Thus, MMSC therapy represents a special type of medical intervention that has both a systemic range of therapeutic efficacy and local activity on 

individual sites of an organ. Over the past decades, MMSC therapy has continuously been in a cautious transition from research development to clinically approved therapies. Clinical trial data has shown that this therapy is rarely associated with severe adverse events, is well tolerated and quite safe in the short-term period. However, it has a number of limitations for use, mainly due to the risk of malignant transformation. The success of stem cell transplantation in the treatment of various diseases has been confirmed both in preclinical studies and in clinical practice. The main issues that arise when assessing the therapeutic efficacy of MMSC-associated therapy are the type of cells (adipogenic, bone marrow, etc.), delivery route, number of cells injected, and the optimal number of injections. There is a growing body of experimental and clinical evidence suggesting that both an adequate delivery route and an adequate dose can increase the likelihood of success of MMSC-associated. Each cell delivery route has costs and benefits. However, there is generally contradictory evidence on the comparative efficacy of different cell delivery routes. The optimal dose of transplanted cells is also debated, as high MMSC doses may increase the risks of complications and may not have the proper effect both when administered systemically and locally. These aspects require further systematization of available data to maximize the effect of cell therapy by selecting the safest and most appropriate approaches.

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The authors declare that there are no conflicts of interest present.