Autologous preconditioned mesenchymal stem cell sheets improve left ventricular function in a rabbit old myocardial infarction model.
Autologous preconditioned mesenchymal stem cell sheets improve left ventricular function in a rabbit old myocardial infarction model.
复制标题
DOI：
--
复制
发表时间：
2016-05
影响因子：
2.2
通讯作者：
Yuya Tanaka;B. Shirasawa;Y. Takeuchi;Daichi Kawamura;Tamami Nakamura;M. Samura;Arata Nishimoto;Koji Ueno;N. Morikage;Tohru Hosoyama;K. Hamano
中科院分区：
文献类型：
--
作者：
Yuya Tanaka;B. Shirasawa;Y. Takeuchi;Daichi Kawamura;Tamami Nakamura;M. Samura;Arata Nishimoto;Koji Ueno;N. Morikage;Tohru Hosoyama;K. Hamano
间充质干细胞(MSCs)是治疗心肌梗死血管生成的最有力工具之一。然而，在严重的缺血性疾病中，由于移植物细胞的保留不良，传统的MSC移植方法导致治疗效果不佳。细胞片技术已经发展成为一种新的方法，即使在缺血组织中也可以延长移植细胞的保留时间。最近，我们证实了低氧预处理可提高心肌梗死小鼠心肌细胞片植入的治疗效果。在这项研究中，我们研究了低氧预处理是否激活了骨髓来源的间充质干细胞(BM-MSC)膜的治疗功能，并改善了自体移植后的兔梗死心脏的心功能。BM-MSC单层膜中血管内皮生长因子(VEGF)的产生增加，在低氧(2%O2)培养48h时达到高峰。为了检测体内效应，将预处理的自体BM-MSC片植入到兔陈旧性心肌梗死模型中。植入预处理的BM-MSC膜可促进梗死区周围血管生成，缩小梗死区面积，改善梗死区的左心功能。重要的是，经处理的BM-MSC片材的治疗效果高于标准培养片材。因此，植入自体预适应的BM-MSC片是一种增强慢性心肌梗死心脏治疗性血管生成的可行方法。
Mesenchymal stem cells (MSCs) constitute one of the most powerful tools for therapeutic angiogenesis in infarcted hearts. However, conventional MSC transplantation approaches result in insufficient therapeutic effects due to poor retention of graft cells in severe ischemic diseases. Cell sheet technology has been developed as a new method to prolong graft cell retention even in ischemic tissue. Recently, we demonstrated that hypoxic pretreatment enhances the therapeutic efficacy of cell sheet implantation in infarcted mouse hearts. In this study, we investigated whether hypoxic pretreatment activates the therapeutic functions of bone marrow-derived MSC (BM-MSC) sheets and improves cardiac function in rabbit infarcted hearts following autologous transplantation. Production of vascular endothelial growth factor (VEGF) was increased in BM-MSC monolayer sheets and it peaked at 48 h under hypoxic culture conditions (2% O2). To examine in vivo effects, preconditioned autologous BM-MSC sheets were implanted into a rabbit old myocardial infarction model. Implantation of preconditioned BM-MSC sheets accelerated angiogenesis in the peri-infarcted area and decreased the infarcted area, leading to improvement of the left ventricular function of the infarcted heart. Importantly, the therapeutic efficacy of the preconditioned BM-MSC sheets was higher than that of standardly cultured sheets. Thus, implantation of autologous preconditioned BM-MSC sheets is a feasible approach for enhancing therapeutic angiogenesis in chronically infarcted hearts.