ГИПОКСИЧЕСКОЕ ПРЕКОНДИЦИОНИРОВАНИЕ СТВОЛОВЫХ КЛЕТОК КАК НОВЫЙ ПОДХОД К ПОВЫШЕНИЮ ЭФФЕКТИВНОСТИ КЛЕТОЧНОЙ ТЕРАПИИ ИНФАРКТА МИОКАРДА

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В последнее десятилетие исследование стволовых клеток развивается ускоренными темпами. Различные типы стволовых клеток использовали для терапии инфаркта миокарда (ИМ). Несмотря на положительный эффект доклинических исследований, успех клинических исследований был незначителен. Существенными препятствиями для регенерации инфарцированного миокарда являются следующие: 1) далеко не каждый тип стволовых клеток может дифференцироваться в кардиомиоциты; 2) низкая выживаемость трансплантированных клеток в суровом микроокружении инфарцированного миокарда. Гипоксическое прекондиционирование (ГП) повышает эффективность трансплантации мезенхимальных стволовых клеток и сердечных клеток-предшественников при терапии экспериментальных моделей инфаркта миокарда. Показано, что трансплантация прекондиционированных стволовых клеток уменьшает размер инфаркта, препятствует постинфарктному ремоделированию сердца, оказывает позитивный эффект на течение экспериментальной ишемической кардиомиопатии. Гипоксическое прекондиционирование предупреждает некроз и апоптоз стволовых клеток в условиях тяжелой длительной гипоксии или окислительного стресса. Защитный эффект ГП связывают с тремя основными процессами: 1) формирование фенотипа клетки, обеспечивающего выживаемость в условиях гипоксии (усиление экспрессии HIF-1α, активация ERK1/2-киназы, Akt-киназы, усиление экспрессия рецепто­ров эритропоэтина и продукция эритропоэтина, повышение уровня антиапоптозных белков Bcl-2 и Bcl-xL); 2) увеличение продукции факторов роста (VEGF, HGF), экспрессии VEGF-2-рецептора и HGF-рецептора; 3) усиление формирования рецепторов CXCR4 и CXCR7, которые обеспечивают хоминг стволовых клеток в зоне ишемии.

 

Об авторах

Л. Н. Маслов

НИИ кардиологии СО РАМН, Томск, Российская Федерация

Автор, ответственный за переписку.
Email: maslov@cardio.tsu.ru
PhD, professor, Head of Laboratory of Experimental Surgery, Federal State Budget Institution “Research Center of Cardiology”, Siberian Department of Russian Academy of Medical Sciences. Address: 111, Kievskaya Street, Tomsk, RF, 634012; tel.: +7 (3822) 26-21-74 Россия

Ю. К. Подоксенов

НИИ кардиологии СО РАМН, Томск, Российская Федерация

Email: uk@cardio-tomsk.ru
PhD, Head of the Department of Anesthesiology and Resuscitation, Federal State Budget Institution “Scientific Research Center of Cardiology”, Siberian Department of Russian Academy of Medical Sciences Address: 111, Kievskaya Street, Tomsk, RF, 634012; tel.: +7 (3822) 26-21-74 Россия

А. Г. Портниченко

Институт физиологии им. А.А. Богомольца, НАН Украины, Киев

Email: port@serv.biph.kiev.ua
MD, senior research scientist of the Department of Common and Molecular Pathophysiology of A.A. Bogomolets Institute of Physiology, National Academy of Sciences, Ukraine Address: 4, Bogomoltsa str., Kiev, Ukraine Украина

А. В. Наумова

Отдел радиологии, Университет Вашингтона, Сиэтл, США

Email: anabella1710@gmail.com
MD, research scientist of the Department of Radiology, Washington University. Address: Seattle, USA США

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