References

mimmun

Медицинская иммунология

Medical Immunology (Russia)

1563-06252313-741X

SPb RAACI

10.15789/1563-0625-MSC-2128

mimmun-2128

Research Article

ОБЗОРЫ

REVIEWS

Мезенхимные стволовые клетки: краткий обзор классических представлений и новых факторов остеогенной дифференцировки

Mesenchymal stem cells: a brief review of classis concepts and new factors of osteogenic differentiation

https://orcid.org/0000-0001-5231-6910

Юрова

К. А.

Yurova

K. A.

к.м.н., научный сотрудник,

г. Калининград

PhD (Medicine), Research Associate,

Kaliningrad

larisalitvinova@yandex.ru

Мелащенко

Е. С.

Melashchenko

E. S.

младший научный сотрудник,

г. Калининград

Junior Research Associate,

Kaliningrad

Хазиахматова

О. Г.

Khasiakhmatova

O. G.

к.б.н., научный сотрудник,

г. Калининград

PhD (Biology), Research Associate,

Kaliningrad

Малащенко

В. В.

Malashchenko

V. V.

научный сотрудник,

г. Калининград

Research Associate,

Kaliningrad

Мелащенко

О. Б.

Melashchenko

O. B.

научный сотрудник,

г. Калининград

Research Associate,

Kaliningrad

Шунькин

Е. О

Shunkin

E. O.

младший научный сотрудник,

г. Калининград

Junior Research Associate,

Kaliningrad

Норкин

И. К.

Norkin

I. K.

аспирант медицинского института,

г. Калининград

Postgraduate Student,

Kaliningrad

Хлусов

И. А.

Khlusov

I. A.

д.м.н., главный научный сотрудник, г. Калининград;

профессор кафедры морфологии и общей патологии, г. Томск;

профессор Исследовательской школы химических и биомедицинских технологий, г. Томск

PhD, MD (Medicine), Chief Research Associate, Kaliningrad;

Professor, Department of Morphology and General Pathology, Tomsk;

Professor, Tomsk

Литвинова

Л. С.

Litvinova

L. S.

д.м.н., директор Центра иммунологии и клеточных биотехнологий

236000, г. Калининград, ул. Гайдара, 6 (каб. 302)

L.S., PhD, MD (Medicine), Director,

Kaliningrad

larisalitvinova@yandex.ru

Центр иммунологии и клеточных биотехнологий ФГАОУ ВО «Балтийский федеральный университет имени И.Канта»РоссияCenter of Immunology and Cellular Biotechnologies, I. Kant Baltic Federal UniversityRussian Federation

Центр иммунологии и клеточных биотехнологий ФГАОУ ВО «Балтийский федеральный университет имени И. Канта»Russian FederationCenter of Immunology and Cellular Biotechnologies, I. Kant Baltic Federal UniversityRussian Federation

ФГАОУ ВО «Балтийский федеральный университет имени И. Канта»Russian FederationMedical Institute, I. Kant Baltic Federal UniversityRussian Federation

Центр иммунологии и клеточных биотехнологий ФГАОУ ВО «Балтийский федеральный университет имени И. Канта»; ФГБОУ ВО «Сибирский государственный медицинский университет» Министерства здравоохранения РФ; ФГАОУ ВО «Национальный исследовательский Томский политехнический университет»Russian FederationCenter of Immunology and Cellular Biotechnologies, I. Kant Baltic Federal University; Siberian State Medical University; Research School of Chemical and Biomedical Technologies, National Research Polytechnic UniversityRussian Federation

Балтийский федеральный университет ФГАОУ ВО «Балтийский федеральный университет имени И. Канта»Russian FederationCenter of Immunology and Cellular Biotechnologies, I. Kant Baltic Federal UniversityRussian Federation

2021

24042021

232207222

2021

Юрова К.А., Мелащенко Е.С., Хазиахматова О.Г., Малащенко В.В., Мелащенко О.Б., Шунькин Е.О., Норкин И.К., Хлусов И.А., Литвинова Л.С.

Yurova K.A., Melashchenko E.S., Khasiakhmatova O.G., Malashchenko V.V., Melashchenko O.B., Shunkin E.O., Norkin I.K., Khlusov I.A., Litvinova L.S.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.mimmun.ru/mimmun/article/view/2128

Молекулярно-генетические механизмы, сигнальные пути, условия, факторы и маркеры остеогенной дифференцировки мезенхимных стволовых клеток (МСК) активно изучаются, несмотря на то, что считаются одними из наиболее исследованных направлений в области клеточных технологий. Во многом это обусловлено накопившимися противоречиями в, казалось бы, классических знаниях, а также постоянным обновлением результатов в анализируемой области. В связи с этим мы сосредоточили внимание на основных классических представлениях и некоторых новых факторах и механизмах, оказывающих заметное регуляторное влияние на дифференцировочный потенциал постнатальных МСК. В обзоре рассматривается значение источника получения МСК для реализации их дифференцировочного потенциала, роль клеточного микроокружения. Освещаются вопросы классификации, терминологии и функциональной активности МСК из различных источников. Описаны молекулярно-генетические факторы и сигнальные пути дифференцировки МСК; рассмотрены как классические участники остеогенеза с описанием их новых функциональных свойств, так и новые молекулы, способные участвовать в процессах костеобразования. Отмечено, что данные об основных генах, задействованных в процессе остеогенеза, крайне противоречивы. Проанализирован паракринный потенциал МСК в механизмах регенерации тканей; отмечено важнейшее значение воспаления в остеогенезе, в частности присутствие в очаге повреждения воспалительных цитокинов и хемокинов, продуцируемых не только клетками микроокружения, но и клетками крови, в том числе мононуклеарными лейкоцитами, мигрирующими в очаг повреждения. Важная роль в настоящем обзоре отведена рассмотрению биомеханических сигналов и особенностей влияния конформационных изменений клеточного цитоскелета (формы клетки) на дифференцировку МСК, так как морфологические особенности клеток и структура цитоскелета модулируется взаимодействием клеточной поверхности с факторами окружающей среды, включая гидростатическое давление, поток жидкости, нагрузка на сжатие/растяжение. Представлены данные о том, что эластичность экстрацеллюлярного матрикса является одним из определяющих факторов клеточной дифференцировки. Сделано заклю чение о необходимости перехода от точечного изучения эффектов отдельных генов к множественным измерениям генно-регуляторного профиля и биомолекул, ответственных за реализацию многочисленных, полностью не изученных остеогенных факторов эндогенного и экзогенного происхождения. Одним из краеугольных направлений в будущих (эпи)генетических исследованиях будет решение вопроса о том, реализуются ли остеомодулирующие эффекты через специфические сигнальные пути и/или имеется перекрестный сигналинг с известными генами остеогенной дифференцировки МСК.

Molecular genetic mechanisms, signaling pathways, cultural conditions, factors, and markers of osteogenic differentiation of mesenchymal stem cells (MSC) are actively studied despite numerous works in this area of cellular technologies. This is largely due to the accumulating contradictions in seemingly classical knowledge, as well as permanent updating of the results in the field. In this regard, we focused on the main classical concepts and some new factors and mechanisms that have a noticeable regulatory effect on the differentiation potential of postnatal MSCs. The present review considers the significance of MSC sources for their differentiation capacity, as well as the role of the cellular microenvironment. The issues of classification, terminology, and functional activity of MSCs from various sources are discussed. The paracrine potential of MSCs in tissue regeneration has been considered; sufficient importance of inflammation in osteogenesis is noted, in particular, the presence of inflammatory cytokines and chemokines in the lesion focus, produced not only by microenvironmental cells but also by blood cells, including mononuclear leukocytes, migrating to the affected site. An important role in this review is given to biomechanical signals and to influence of conformational changes in cell cytoskeleton (cell shape) upon MSC differentiation, since the morphological features of cells and the structure of cytoskeleton are modulated by interactions of the cell surface with environmental factors, including hydrostatic pressure, fluid flow, compression/stretching loads. The data are presented concerning elasticity of extracellular matrix being a determining factor of cell differentiation. We conclude that one should switch from point studies of individual gene effects to multiple measurements of the gene-regulatory profile and biomolecules responsible for multiple, still poorly studied osteogenic factors of endogenous and exogenous origin. Among cornerstones in future (epi)genetic studies will be to decide if osteomodulatory effects are realized through specific signaling pathways and/or via cross-signaling with known genes controlling osteogenic differentiation of MSCs.

источник клетокгеныфакторы транскрипциимаркеры дифференцировкицитокины и хемокинымеханотрансдукция

cell sourcegenestranscription factordifferentiation markerscytokineschemokinesmechanotransduction

Работа выполнена при финансовой поддержке Совета по грантам Президента Российской Федерации (НШ-2495.2020.7; СП-4193.2021.4).

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