【摘 要】
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Aim Aging is an independent risk factor for heart disease, however the effective intervention has not been found so far.Bone marrow mesenchymal stem cells (BMSCs) have been shown to offer a wide varie
【机 构】
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Department of Pharmacology and Key Laboratory of Cardiovascular Medicine Research,Ministry of Educat
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Aim Aging is an independent risk factor for heart disease, however the effective intervention has not been found so far.Bone marrow mesenchymal stem cells (BMSCs) have been shown to offer a wide variety of cellular functions including the protective effects on damaged hearts.Here we investigated the antiaging properties of BMSCs and the underlying mechanism in a cellular model of cardiomyocyte senescence and a rat model of aging hearts.Methods In vitro study, neonatal rat ventricular cells (NRVCs) and BMSCs were cocultured in the same dish with a semipermeable membrane to separate the two populations.In vivo, the BMSCs were injected into the rat hearts to observe their antiaging effects.The expression of βgalactosidase and agingrelated proteins, and the levels of oxidative stress were determined in vivo and in vitro.The heart function was measured by the HighResolution Imaging System.Results Monocultured NRVCs displayed the senescenceassociated phenotypes, characterized by an increase in the number of βgalactosidasepositive cells and decreases in the degradation and disappearance of cellular organelles in a timedependent manner.The levels of reactive oxygen species and malondialdehyde were elevated, whereas the activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase were decreased, along with upregulation of p53, p21cip1/waf1, and p16INK4a in the aging cardiomyocytes.These deleterious alterations were abrogated in aging NRVCs cocultured with BMSCs.Qualitatively, the same senescent phenotypes were consistently observed in aging rat hearts.Notably, BMSC transplantation significantly prevented these detrimental alterations and improved the impaired cardiac function in the aging rats.Conclusions BMSCs possess strong antisenescence action on the aging NRVCs and hearts and can improve cardiac function after transplantation in aging rats.The present study, therefore, provides an alternative approach for the treatment of heart failure in the elderly population.
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