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Эмбриональные стволовые клетки и клетки костного мозга
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Эмбриональные стволовые клетки и клетки костного мозга

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by admin21.07.2014
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Миогенные стволовые клетки, способные дифференцироваться в кардиомиоциты, можно разделить на две категории: эмбриональные стволовые клетки и стволовые клетки взрослого, находящиеся в костном мозге. ЭС клетки, которые получают из внутреннего клеточного массива эмбриона на стадии бластоцисты, характеризуются способностью к неограниченной и недифференцированной пролиферации.

Они также являются плюрипотентными, что обозначает способность дифференцироваться в любой тип соматической клетки взрослого организма. Поэтому эти клетки могут быть идеальным источником для восстановления поврежденного миокарда. ЭС клетки мыши формируют in vitro агрегат, имеющий название эмбриональные тела. Обычно в пределах 10 дней от 80 до 100% этих клеток имеют спонтанно сокращающиеся участки, но фракция сокращающихся участков небольшая. Несколько групп сообщили о методах генерирования чистых культур кардиомиоцитов. По данным Klug и соавторов, более 99% очищенных, культивированных и генетически отобранных кардиомиоцитов мыши формируют стабильные внутрисердечные трансплантаты с нормальной структурой миокарда.

После их трансплантации в сердце здоровой мыши выявляется формирование интерполированных дисков и щелевидных соединений. Подобно ЭС клеткам мыши, ЭС клетки человека также характеризуются бессмертием, экспрессией специфических факторов транскрипции и поверхностных клеточных молекул, а также способностью к дифференцированию в любой тип клеток. Плюрипотентные стволовые клетки экспрессируют разнообразные рецепторы для факторов роста. В частности, трансформирующий фактор роста и активин-А способствуют дифференциации в мезодермальные производные, такие как мышечные клетки. Также можно достичь дифференциации кардиомиоцитов из ЭС клеток человека, а также электрического сопряжения и синхронного сокращения кардиомиоцитов, полученных из стволовых клеток человека, с кардиомиоцитами крысы в совместной культуре.

На моделях инфаркта в сердце крысы имплантированные ЭС клетки выживали и дифференцировались в зрелые кардиомиоциты через 6 недель после трансплантации. В результате улучшалась функция сердца. Более того, в недавнем исследовании сообщалось, что это улучшение сохранялось длительное время. Несомненно, что эти исследования свидетельствуют о существенных возможностях ЭС клеток для клеточной терапии при сердечной недостаточности. Теоретически ЭС клетки характеризуются как неограниченный источник кардиомиоцитов, даже у человека. Пересаженные ЭС клетки также могут формировать электрическое сопряжение с кардиомиоцитами хозяина и улучшать глобальную функцию сердца. Но, справедливости ради, для клинического применения ЭС клеток у человека все еще остается преодолеть немало серьезных проблем. Во-первых, аллогенное происхождение этих клеток порождает иммунологические проблемы.

В таком случае могут требоваться стратегии, направленные против отторжения, включая иммуносупрессивные препараты. Во-вторых, должны быть оптимизированы эффективность и культуральные условия для дифференциации кардиомиоцитов.

В-третьих, «неразборчивость» недифференцированных стволовых клеток, которые могут формировать и другие типы клеток, чем кардиомиоциты, является громадным преимуществом, но также может вызвать туморогенность. И, последнее, но не менее существенное. Как и относительно кардиомиоцитов плода и новорожденного, серьезным препятствием на пути клинического применения могут стать моральные и этические проблемы.

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