Bone Marrow Mesenchymal Stem Cell Transplantation Retards the Natural Senescence of Rat Hearts
Bone Marrow Mesenchymal Stem Cell Transplantation Retards the Natural Senescence of Rat Hearts
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DOI：
10.5966/sctm.2014-0206
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发表时间：
2015-04
影响因子：
6
通讯作者：
Mingyu Zhang;Di Liu;Shuang Li;Lingling Chang;Yu Zhang;Ruixue Liu;Fei Sun;Wenqi Duan;Weijie Du;Yanping Wu;Tianyang Zhao;Chaoqian Xu;Yanjie Lu
中科院分区：
文献类型：
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作者：
Mingyu Zhang;Di Liu;Shuang Li;Lingling Chang;Yu Zhang;Ruixue Liu;Fei Sun;Wenqi Duan;Weijie Du;Yanping Wu;Tianyang Zhao;Chaoqian Xu;Yanjie Lu
骨髓间充质干细胞（BMSCs）已被证明具有多种细胞功能，包括对受损心脏的保护作用。在心肌细胞衰老模型和大鼠心脏衰老模型中，我们研究了骨髓间充质干细胞的抗衰老特性及其潜在机制。用半透膜将新生大鼠心室细胞（NRVCs）与骨髓间充质干细胞（BMSCs）在同一培养皿中共培养。单次培养的nrvc表现出衰老相关的表型，其特征是β -半乳糖苷酶阳性细胞数量增加，细胞器降解和消失减少，并以时间依赖性的方式存在。衰老心肌细胞中活性氧和丙二醛水平升高，抗氧化酶超氧化物歧化酶和谷胱甘肽过氧化物酶活性降低，p53、p21Cip1/Waf1和p16INK4a表达上调。在与骨髓间充质干细胞共培养的衰老nrvc中，这些有害的改变被消除。定性地说，在衰老的大鼠心脏中一致观察到相同的衰老表型。值得注意的是，骨髓间充质干细胞移植显著地阻止了这些有害的改变，并改善了衰老大鼠受损的心功能。综上所述，骨髓间充质干细胞对衰老大鼠nrvc和心脏具有较强的抗衰老作用，移植后可改善心脏功能。因此，本研究为老年人群心力衰竭的治疗提供了另一种方法。
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, 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. 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.