Аннотация
Образование рубца при нормальной регенерации поврежденных тканей у взрослых может приводить к заметным косметическим и функциональным дефектам органов и существенно влиять на качество жизни. Напротив, известно, что ткани плода до третьего триместра беременности способны к полной регенерации с восстановлением исходной архитектуры и функциональной активности. Понимание клеточных и молекулярных механизмов регенерации ран плода создаст основу для разработки успешного лечения, направленного на минимизацию рубцевания. Мезенхимальные стромальные клетки (МСК) играют важную роль в восстановлении тканей, поскольку секретируемые ими цитокины, хемокины, факторы роста и внеклеточные везикулы участвуют в регуляции миграции, ангиогенеза, синтеза и ремоделирования внеклеточного матрикса. Мезодермальная дифференцировка индуцированных плюрипотентных стволовых клеток человека (ИПСК) позволяет воспроизвести последовательные этапы эмбриогенеза in vitro и создать изогенные клеточные модели МСК, соответствующие разным стадиям развития человека. В данной работе в результате специфически направленной многостадийной мезодермальной дифференцировки ИПСК были получены изогенные линии клеток примитивной полоски, латеральной и параксиальной мезодермы и проведен сравнительный анализ их экспрессионных профилей. Показано, что полученные клетки латеральной мезодермы (ЛМ) и параксиальной мезодеры (ПМ), являются предшественниками для МСК. МСК, полученные в результате дифференцировки клеток как ЛМ, так и ПМ, обладали сходным профилем по экспрессии панмезодермальных маркеров. Сравнительный анализ функциональной активности МСК и их предшественников в провоспалительном микроокружении позволит получить молекулярные инструменты для лучшего понимания фундаментальных механизмов регенерации тканей плода и определить терапевтические мишени для минимизации рубцевания и патологических процессов, характеризующихся чрезмерной фиброплазией.
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