БИОХИМИЯ, 2020, том 85, вып. 9, с. 1240–1255

УДК 57.085.23

Репрограммирование клеток с сохранением эпигенетического возраста: преимущество или ограничение?

Обзор

© 2020 Е.М. Самойлова *, В.П. Баклаушев

Федеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий ФМБА России, 115682 Москва, Россия; электронная почта: samoyket@gmail.com

Поступила в редакцию 28.07.2020
После доработки 28.07.2020
Принята к публикации 05.08.2020

DOI: 10.31857/S0320972520090055

КЛЮЧЕВЫЕ СЛОВА: регенеративная медицина, эпигенетические часы, прямое репрограммирование, индуцированные плюрипотентные стволовые клетки, эмбриональные стволовые клетки, теломеры, метилом.

Аннотация

С момента первого описания старения и возраста клеток Хейфликом и Мурхедом в 1961 году наше понимание этих процессов значительно расширилось. Помимо укорочения теломерных концов, колоссальное значение в процессе старения имеют эпигенетические изменения профиля метилирования ДНК. В аспекте создания технологии репрограммирования клеток вопросы эпигенетического возраста и процесса старения приобретают особую актуальность. Два принципиально различных подхода к репрограммированию: создание клеток с индуцированной плюрипотентностью (ИПСК) и прямая трансдифференцировка по-разному влияют на эпигенетический возраст клетки. Считается, что при получении ИПСК возраст клетки, в частности профиль метилирования ДНК, «обнуляется», а при прямой трансдифференцировке – сохраняется. Понимание биологической роли метилирования ДНК в развитии, поддержании функциональной активности, тканевом и клеточном разнообразии, модификациях нейронных сетей в процессе обучения и в инволюционных процессах, сопровождающих старение, крайне важно для создания адекватных моделей заболеваний нервной системы. Прямое репрограммирование является и альтернативой, и ценным дополнением к методике ИПСК как источник зрелых клеток для моделирования нейродегенеративных заболеваний, а также в качестве новой стратегии для in vivo заместительной терапии. Оптимизация технологии получения аутологичных клеток пациентов с использованием альтернативных методов прямого и непрямого репрограммирования с учётом состояния эпигенетических часов первичных клеток будет способствовать дальнейшему развитию регенеративной и персонифицированной медицины.

Сноски

* Адресат для корреспонденции.

Финансирование

Работа выполнена при финансовой поддержке Российского фонда фундаментальных исследований (грант № 19-115-50396).

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

Соблюдение этических норм

Настоящая статья не содержит описания выполненных авторами исследований с участием людей или использованием животных в качестве объектов.

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