ТРАНСПЛАНТАЦИЯ ГЕНЕТИЧЕСКИ МОДИФИЦИРОВАННЫХ СТВОЛОВЫХ КЛЕТОК, ПОВЫШЕННО ЭКСПРЕССИРУЮЩИХ ТЕРАПЕВТИЧЕСКИЕ РОСТОВЫЕ ФАКТОРЫ,ПРИ ЛЕЧЕНИИ ЭКСПЕРИМЕНТАЛЬНОГО ИНФАРКТА МИОКАРДА КРЫС

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Мы проанализировали гипотезу, что одновременная трансгенная модификация трансплантируемых стволовых клеток 4-мя ростовыми факторами активирует разнообразные сигнальные механизмы для выживания введенных клеток, а также мобилизацию различных стволовых/прогениторных клеток для кардиогенеза при терапии инфаркта миокарда. Плазмиды, несущие гены, кодирующие IGF-1, VEGF, SDF-1α и HGF, были сконструированы и трансфицированы в скелетные миобласты (SM) крыс. Повышенная экспрессия ряда факторов в трансфицированных SM (TransSM) была подтверждена методами ПЦР, Вестерн-блоттинга (ВБ) и иммунофлюоресцентного окрашивания. Кондиционная среда от TransSM обладала цитопротекторными свойствами для кардиомиоцитов в условиях окислительного стресса, стимулировала миграцию клеток HUVEC, и усиливала ангиогенез клеток HUVEC in vitro . Интрамиокардиальная трансплантация 1,5×106 TransSM продемонстрировала обширную мобилизацию стволовых/прогениторных клеток в инфарктном миокарде и улучшала интегрирование TransSM в сердце. Экстенсивный неомиогенез и ангиогенез наблюдался через8 недель после трансплантации. Итак, одновременная активация разнообразных сигнальных механизмов благодаря повышенной экспрессии нескольких ростовых факторов вызывает массовую мобилизацию и хоминг как стволовых/прогениторных клеток из костного мозга и циркулирующих в крови, так и резидентных кардиальных стволовых клеток, что приводит к ускоренной репарации инфарктного миокарда.

Об авторах

Михаил Анатольевич Коноплянников

ФГБУ ФНКЦ ФМБА России

Email: mkonopl@mail.ru
заведующий лабораторией клеточных технологий ФГБУ ФНКЦ ФМБА России, к.б.н.

Х Х Хайдер

Cardiovascular Diseases Center, USA

Associate Professor, Cardiovascular Diseases Center, University of Cincinnati, Cincinnati OH, USA.

М Ашраф

Cardiovascular Diseases Center, USA

Professor, Cardiovascular Diseases Center, University of Cincinnati, Cincinnati OH, USA.

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© Коноплянников М.А., Хайдер Х.Х., Ашраф М., 2013

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