title: Bone marrow mesenchymal stem cell transplantation retards the natural senescence of rat hearts.
abstract: 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. Neonatal rat ventricular cells (NRVCs) and BMSCs were cocultured in the same dish with a semipermeable membrane to separate the two populations. Monocultured NRVCs displayed the senescence-associated phenotypes, characterized by an increase in the number of β-galactosidase-positive cells and decreases in the degradation and disappearance of cellular organelles in a time-dependent 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, p21(Cip1/Waf1), and p16(INK4a) 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. In summary, 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.
authors: Department of Pharmacology and Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, State Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors: Mingyu
authors: M
authors: Zhang
authors: Department of Pharmacology and Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, State Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors: Di
authors: D
authors: Liu
authors: Department of Pharmacology and Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, State Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors: Shuang
authors: S
authors: Li
authors: Department of Pharmacology and Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, State Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors: Lingling
authors: L
authors: Chang
authors: Department of Pharmacology and Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, State Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors: Yu
authors: Y
authors: Zhang
authors: Department of Pharmacology and Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, State Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors: Ruixue
authors: R
authors: Liu
authors: Department of Pharmacology and Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, State Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors: Fei
authors: F
authors: Sun
authors: Department of Pharmacology and Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, State Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors: Wenqi
authors: W
authors: Duan
authors: Department of Pharmacology and Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, State Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors: Weijie
authors: W
authors: Du
authors: Department of Pharmacology and Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, State Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors: Yanping
authors: Y
authors: Wu
authors: Department of Pharmacology and Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, State Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors: Tianyang
authors: T
authors: Zhao
authors: Department of Pharmacology and Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, State Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
authors: Chaoqian
authors: C
authors: Xu
authors: Department of Pharmacology and Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, State Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China yjlu86@gmail.com.
authors: Yanjie
authors: Y
authors: Lu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D016922:Cellular Senescence; D006333:Heart Failure / Q000473:pathology / Q000628:therapy*; D006352:Heart Ventricles / Q000473:pathology / Q000637:transplantation; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D009203:Myocardial Infarction / Q000628:therapy; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D051381:Rats
keywords: Bone marrow mesenchymal stem cells; Heart; Reactive oxygen species; Senescence; p53