Стимуляция ангио/миогенеза при сердечно-сосудистой патологии с использованием генной терапии и аутотрансплантации клеток-предшественников тема диссертации и автореферата по ВАК РФ 14.01.24, доктор биологических наук Еремеева, Марина Викторовна

• Еремеева, Марина Викторовна
• доктор биологических наук
• 2010

Введение диссертации (часть автореферата) на тему «Стимуляция ангио/миогенеза при сердечно-сосудистой патологии с использованием генной терапии и аутотрансплантации клеток-предшественников»

ИНЛС - индекс нарушения локальной сократимости левого желудочка; иРНК - ингибирующая рибонуклеиновая кислота; КМК - костномозговые клетки; КМЦ - кардиомиоцит.

КП - клетки- предшественники (аутологичные); МСК - мезенхимальные стволовые клетки; ОФЭТ - однофотонная эмиссионная томография; ПИКВ(01М1) - прямое интрамиокардиальное введение; ПЭТ - позитронно-эмиссионная томография; РФП - радиофармпрепарат;

ТЛБАП - транслюминальная баллонная ангиопластика; УЗДГ - ультразвуковая допплерография сосудов; ХИНК- хроническая ишемия нижних конечностей; ЦЭК - циркулирующие эндотелиальные клетки; ЦЭП - циркулирующие эндотелиальные клетки-предшественники; ЭКП - эндотелиальные клетки предшественники; ЭСК - эмбриональные стволовые клетки;

ОГЛАВЛЕНИЕ

СПИСОК СОКРАЩЕНИИ

ОГЛАВЛЕНИЕ 3

ВВЕДЕНИЕ 7

Заключение диссертации по теме «Трансплантология и искусственные органы», Еремеева, Марина Викторовна

Выводы

1. Активизация восстановительных процессов в ишемизированных тканях достигается путем индукции в них процессов ангио/миогенеза, которые могут быть усилены применением ангиогенезстимулирующих факторов.

2. Созданная плазмидная конструкция ангиогенного препарата - ангиостимулин -биосовместима, нетоксична, позволяет эффективно экспрессировать ген УЕСТ7165, и может быть использована для индукции репаративного ангиогенеза в ишемизированных тканях.

3. Высокоочищенная популяция СБ133+ стволовых клеток костного мозга состоит из двух субпопуляций: менее зрелых СВ133"7СВ347УЕОП1-2+ клеток и более дифференцированных СЭ1337СВ34+/УЕОР11-2+ клеток, причем субпопуляция С0133+/СВ347УЕ0РК-2+ клеток обладает более высоким потенциалом дифференцировки в направлении неоангиогенеза.

4. Клетки СВ133+ обладают более выраженной ангиогенной активностью по сравнению с СБ34+, и поэтому именно эти клетки должны использоваться для стимуляции ангиогенеза при лечении ишемической болезни сердца и хронической ишемии нижних конечностей.

5. Препарат «ангиостимулин» улучшает перфузию миокарда в наиболее пораженных ишемией сегментах и этот эффект сохраняется не менее года.

6. При сравнительной оценке эффективности способов введения аутологичных костномозговых клеток-предшественников С0133+ для стимуляции регенеративных процессов в миокарде, показано что при интрамиокардиальном введении отмечается достоверное улучшение перфузии в леченных сегментах с исходно умеренным и значительным снижением перфузии. При интракоронарном способе введения достоверных изменений показателей перфузии получено не было.

7. Как при артериальном, так и при внутримышечном введении аутологичных клеток-предшественников СБ133+ или гена УЕОРк,5 зарегистрировано образование новой сосудистой сети при лечении ХИНК.

8. После аутотрансплантации клеток-предшественников С1Э133+ достоверно улучшалось качество жизни больных ИБС и ХИНК.

Практические рекомендации

Исходя из результатов проведенных исследований представляется целесообразным применение внутримышечного введения УЕОР (ангиостимулина) при ишемии миокарда и хронической ишемии нижних конечностей (с учетом критериев включения и исключения пациентов).

Использование аутологичных костномозговых клеток-предшественников СБ133+ можно рекомендовать для лечения сердечной недостаточности в сочетании с хирургическими методами, при этом наиболее эффективным является метод изолированного интрамиокардиалыюго введения.

При лечении ХИНК можно рекомендовать как внутриартериальное, так и в/мышечное введение аутологичных клеток-предшественников СБ133+ или ангиостимулина (гена УЕОР^)

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