regmedjournalРегенерация органов и тканейРегенерация органов и тканей2949-5938Общество регенеративной медицины10.60043/2949-5938-2023-2-7-32regmedjournal-34Research ArticleОБЗОРЫ И КОММЕНТАРИИREVIEWS AND COMMENTSСовременные подходы к созданию 2Dи 3D-клеточных моделей для изучения фиброза легкихModern approaches to the creation of 2D and 3D cellular models for the study of lung fibrosisТолстолужинскаяА. Е.TolstoluzhinskayaA. E.

Толстолужинская Анастасия Евгеньевна  — лаборант-исследователь лаборатории репарации и регенерации тканей Института регенеративной медицины Медицинского научно-образовательного центра ; лаборант-исследователь НИЛ генных и клеточных технологий факультета фундаментальной медицины 

119192, г. Москва, Ленинские горы, 1

Anastasiya E. Tolstoluzhinskaya— research laboratory assistant at the Laboratory of Tissue Repair and Regeneration of the Institute for Regenerative Medicine of the Medical Scientific and Educational Center ; a research laboratory assistant at the Institute of Gene and Cell Technologies of the Faculty of Medicine

Moscow, Leninskie Gory, 1, 119991

tolstoluzhinskayaae@my.msu.ruБасаловаН. А.BasalovaN. A.

Басалова Наталия Андреевна — к.б.н., м.н.с. лаборатории репарации и регенерации тканей Института регенеративной медицины Медицинского научно-образовательного центра ; м.н.с. НИЛ генных и  клеточных технологий факультета фундаментальной медицины

119192, г. Москва, Ленинские горы, 1

Nataliya A. Basalova— Ph.D. of Biological Sciences, junior research assistant of the Laboratory of Tissue Repair and Regeneration of the Institute for Regenerative Medicine of the Medical Scientific and Educational Center ; junior research assistant of the Research Institute of Gene and Cellular Technologies of the Faculty of Medicine

Moscow, Leninskie Gory, 1, 119991

ЕфименкоА. Ю.EfimenkoA. Y.

Ефименко Анастасия Юрьевна — к.м.н., заведующий лабораторией репарации и регенерации тканей Института регенеративной медицины Медицинского научно-образовательного центра ; доцент кафедры биохимии и регенеративной биомедицины факультета фундаментальной медицины

119192, г. Москва, Ленинские горы, 1

Anastasiya Y. Efimenko— M.D., Ph.D., head of the Laboratory of Tissue Repair and Regeneration of the Institute for Regenerative Medicine of the Medical Research and Educational Center ; Associate Professor of the Department of Biochemistry and Regenerative Biomedicine of the Faculty of Medicine

Moscow, Leninskie Gory, 1, 119991

ФГБОУ ВО «Московский государственный университет имени М.В. Ломоносова»РоссияLomonosov Moscow State UniversityRussian Federation20230207202412732Copyright © Толстолужинская А.Е., Басалова Н.А., Ефименко А.Ю., 20242024Толстолужинская А.Е., Басалова Н.А., Ефименко А.Ю.Tolstoluzhinskaya A.E., Basalova N.A., Efimenko A.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.regmed-journal.ru/jour/article/view/34

Фиброз легких является следствием многих воздействий, ведущих к повреждению ткани легкого и развитию последующего воспаления. Фиброз представляет собой разрастание соединительной ткани, которое может приводить к нарушению архитектоники легких и снижать их функциональность вплоть до летального исхода. При этом в настоящее время механизмы, лежащие в основе фиброгенеза, недостаточно изучены. В связи с этим задача по их изучению не теряет своей актуальности, и для ее решения требуется разработка моделей фиброза легких, способных отразить все ключевые процессы фиброгенеза. Модель in vivo с  использованием животных обладает множественными неоспоримыми преимуществами, но при этом имеет строгие этические ограничения и  не отражает всех механизмов фиброза легких, свойственных человеческому организму. При этом в исследованиях in vitro ученые могут позволить себе использовать биоматериалы не только животных, но и человека и на их основе строить клеточные системы — от 2Dдо 3D-моделей. Моделирование фиброза легких преимущественно основано на использовании основных типов клеток, вовлеченных в  развитие фиброза легких, таких как миофибробласты, фибробласты, альвеолоциты и других. Некоторые модели базируются также на специфическом фиброз-ассоциированном внеклеточном матриксе и дальнейшем изучении взаимодействия клеток как друг с другом, так и с матриксом. Cтоит учитывать, что в  разных моделях отображаются естественных процессов фиброгенеза, что требует от исследовательского сообщества использования широкого круга моделей. Учитывая многофакторность патогенеза фиброза легких, важно понимать всю совокупность происходящих процессов для получения полноты реальной картины, близкой к картине in vivo, в связи с чем важна многокомпонентность моделей. В  данном обзоре акцентировано внимание на анализе различных моделей фиброза легких in vitro в двумерных и трехмерных системах, отображены подходы к их созданию, ключевые различия, основные преимущества и  недостатки моделей, как частные, так и общие.

Lung fibrosis is a consequence of many influences leading to damage to lung tissue and the development of subsequent inflammation. Fibrosis is an overgrowth of connective tissue, which can lead to a violation of the architectonics of the lungs and reduce their functionality up to a fatal outcome. At the same time, the mechanisms underlying fibrogenesis are currently insufficiently studied. In this regard, the task of studying them does not lose its relevance, and its solution requires the development of models of lung fibrosis that can reflect all the key processes of fibrogenesis.

The in vivo model using animals has multiple undeniable advantages, but at the same time it has strict ethical limitations and does not reflect all the mechanisms of lung fibrosis inherent in the human body. At the same time, in vitro research, scientists can afford to use biomaterials not only of animals, but also of humans, and build cellular systems based on them — from 2D to 3D models. Modeling of pulmonary fibrosis is mainly based on the use of the main types of cells involved in the development of pulmonary fibrosis, such as myofibroblasts, fibroblasts, alveolocytes and others. Some models are also based on a specific fibrosis-associated extracellular matrix and further study of the interaction of cells with each other and with the matrix. It should be borne in mind that different models display individual nuances of the native processes of lung fibrogenesis, which requires the research community to use a wide range of models. Taking into account the multifactorial pathogenesis of pulmonary fibrosis, it is important to understand the totality of the processes taking place in order to obtain the completeness of the real picture, close to the picture in vivo, and therefore the multicomponence of models is important. This review focuses on the analysis of various models of lung fibrosis in vitro in two-dimensional and three-dimensional systems, shows approaches to their creation, key differences, main advantages and disadvantages of models, both particular and general.

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