Трехмерные модели культур клеток: способы получения и характеристика основных моделей

В течение многих лет золотым стандартом в исследованиях злокачественных новообразований являлись культуры опухолевых клеток in vitro, ксенотрансплантаты in vivo или генетически модифицированные модели животных. К настоящему времени арсенал инструментов современных медико-биологических исследований пополнился трехмерными клеточными моделями (3D-культуры). 3D-культуры воспроизводят тканеспецифичные характеристики топологии ткани, что делает их релевантными тканевыми моделями с точки зрения клеточной дифференцировки, метаболизма и развития лекарственной устойчивости. Благодаря своему потенциалу такие модели уже применяются многими исследовательскими группами как для фундаментальных, так и для трансляционных исследований, и их использование позволяет значительно сократить количество экспериментов на животных, например, в области онкологии. В литературе 3D-культуры классифицируют по технике формирования (с каркасом/без каркаса), условиям культивирования (статические/динамические), а также по клеточной организации и функциям. По клеточной организации 3D-культуры разделяют на «сфероидные модели», «органоиды», «органы-на-чипе» и «микроткани». При этом каждая из моделей имеет свои характерные особенности, которые необходимо учитывать при использовании модели в эксперименте. Наиболее простые 3D-культуры – это «сфероидные модели», представляющие собой плавающие сферические агрегаты клеток. Более сложной 3D-моделью является «органоид» – самоорганизующаяся трехмерная структура, сформированная из стволовых клеток, способных к самообновлению и дифференцировке в составе модели. Микрофлюидные системы «орган-на-чипе» – это чипы, имитирующие in vitro основные физические и биологические процессы в органах и тканях в динамике. «Сфероиды» и «органоиды» за счет объединения различных типов клеток в единую структуру могут быть основой для формирования «микроткани» – гибридной 3D-модели, воспроизводящей специфический тканевый фенотип и содержащей тканеспецифичные компоненты внеклеточного матрикса. В данном обзоре представлена краткая история развития метода культивирования клеток in vitro в 3D-формате, описаны основные характеристики и перспективы применения «сфероидных моделей», «органоидов», «органовна-чипе» и «микротканей» для исследований в области иммуноонкологии солидных опухолей.

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