Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC10310.15690/vramn.v68i12.855РATHOPHYSIOLOGY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ПАТОФИЗИОЛОГИИHYPOXIC PRECONDITIONING OF STEM CELLS AS A NEW APPROACH TO INCREASE THE EFFICACY OF CELL THERAPY FOR MYOCARDIAL INFARCTIONГИПОКСИЧЕСКОЕ ПРЕКОНДИЦИОНИРОВАНИЕ СТВОЛОВЫХ КЛЕТОК КАК НОВЫЙ ПОДХОД К ПОВЫШЕНИЮ ЭФФЕКТИВНОСТИ КЛЕТОЧНОЙ ТЕРАПИИ ИНФАРКТА МИОКАРДАMaslovL. N.МасловЛ. Н.
Russian Federation

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

maslov@cardio.tsu.ruPodoksenovYu. K.ПодоксеновЮ. К.
Russian Federation

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

uk@cardio-tomsk.ruPortnichenkoA. G.ПортниченкоА. Г.
Ukraine

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

port@serv.biph.kiev.uaNaumovaA. V.НаумоваА. В.
United States

MD, research scientist of the Department of Radiology, Washington University. Address: Seattle, USA

anabella1710@gmail.comResearch Institute for Cardiology of Siberian Branch under the Russian Academy of Medical Sciences, Tomsk, Russian FederationНИИ кардиологии СО РАМН, Томск, Российская ФедерацияBogomoletz Institute of Physiology National Academy of Sciences of Ukraine, KievИнститут физиологии им. А.А. Богомольца, НАН Украины, КиевDepartment of Radiology, University of Washington, Seattle, USAОтдел радиологии, Университет Вашингтона, Сиэтл, США101220136812Vestnik Rossiiskoi akademii medetsinskikh nauk / Annals of the Russian academy of medical sciencesВестник Российской академии медицинских наук162507082015Copyright ©; 1970, "Paediatrician" Publishers LLCCopyright ©; 1970, Издательство "Педиатръ"1970"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/103

During the last decade, stem cell research has developed at an accelerated pace. Various types of stem cells have been tested for myocardial infarction therapy. Despite the preclinical benefits of cell therapy success in clinical trials remains modest. The main obstacles to regeneration of the infarcted heart using stem cells are: 1) not every stem cell type can differentiate into cardiomyocytes; and 2) low survival rates of transplanted cells, due to the harsh environment of the infarcted myocardium. Hypoxic preconditioning (HP) has been shown to improve transplantation efficacy of mesenchymal stem cells and cardiac progenitor cells in animal models of myocardial infarction. It has also been shown that transplantation of preconditioned cells decreases infarct size, prevents postinfarction remodeling of the heart, and positively modulates development of ischemic cardiomyopathy. Hypoxic preconditioning also prevents extensive death of transplanted cells due to necrosis and apoptosis during long-term hypoxia or oxidative stress. The protective effect of HP is based on three main processes: (1) modification of cell phenotypes to help survival during hypoxia (enhancement of HIF-1α expression, ERK1/2 and Akt activation, enhancement of erythropoietin receptor expression and erythropoietin production, and an elevation in levels of antiapoptotic proteins Bcl-2 and Bcl-xL); (2) upregulation of various secretable factors including the vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), and expression of VEGF-2 and HGF-receptors; (3) enhancement in the formation of CXCR4 and CXCR7 receptors, which play an important role in mobilization and homing of stem cells in the ischemic region.

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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.

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