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脂多糖预处理的骨髓干细胞作为心肌梗死的潜在治疗方法。

LPS-pretreated bone marrow stem cells as potential treatment for myocardial infraction.

机构信息

Department of Thoracic and Cardiovascularm surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China, 210029.

出版信息

Front Biosci (Landmark Ed). 2012 Jan 1;17(4):1294-303. doi: 10.2741/3987.

DOI:10.2741/3987
PMID:22201804
Abstract

The purpose of this study is too investigate the distribution, the number, and the survival time of rat bone marrow mesenchymal stem cells (BMSCs), implanted in rats with myocardial infarction (MI), that were initially pretreated with low dose of LPS. Adult rats were randomly divided into control group, the MI group, 0.1, 1 and 5 mg/kg LPS-pretreated groups. Following the injection of CM-Dil labeled into the mid left anterior descending coronary artery ligation in the left ventricle wall, the number and survival time of red fluorescent labeled BMSCs were determined in the myocardial infarction 48h, 1, 3, and 4 weeks post-injection.. In addition, BMSC cell survival and apoptosis as well as the expression of associated proteins were also studied. After 1 week, the number of red fluorescent cells decreased significantly in MI group and 0.1mg/kg LPS groups, and the decrease was more obvious in 5mg/kg LPS group. However, a large number of BMSCs was apparent in 1mg/kg LPS group, the survival of positive cells was higher than MI group (P less than 0.05), part of the transplanted stem cells migrated into the injured area of the myocardial tissue, and in the injury centers more cardiac stem cells were grouped together. Following 3-4 weeks post-implantation of BMSCs, fluorescence almost disappeared in MI group , while it was still present and scattered in 1mg/kgLPS. Furthermore, while BMSCs showed low survival rate in the MI group, reduced apoptosis was observed in low-dose LPS groups.

摘要

本研究旨在探讨经小剂量 LPS 预处理的骨髓间充质干细胞(BMSCs)在大鼠心肌梗死(MI)模型中的分布、数量和存活时间。成年大鼠随机分为对照组、MI 组、0.1、1 和 5mg/kg LPS 预处理组。在左心室壁的中左前降支冠状动脉结扎部位注射 CM-Dil 标记物后,于注射后 48h、1、3 和 4 周,测定心肌梗死区红色荧光标记 BMSCs 的数量和存活时间。此外,还研究了 BMSC 细胞的存活和凋亡以及相关蛋白的表达。1 周后,MI 组和 0.1mg/kg LPS 组红色荧光细胞数量明显减少,5mg/kg LPS 组减少更为明显。然而,1mg/kg LPS 组可见大量 BMSCs,阳性细胞的存活率高于 MI 组(P 小于 0.05),部分移植的干细胞迁移到心肌组织损伤区,在损伤中心更多的心脏干细胞聚集在一起。BMSCs 植入 3-4 周后,MI 组荧光几乎消失,而 1mg/kg LPS 组仍存在且分散。此外,在 MI 组中 BMSCs 存活率较低,而在低剂量 LPS 组中观察到细胞凋亡减少。

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LPS-stimulated inflammatory environment inhibits BMP-2-induced osteoblastic differentiation through crosstalk between TLR4/MyD88/NF-κB and BMP/Smad signaling.脂多糖刺激的炎症环境通过Toll样受体4/髓样分化因子88/核因子κB与骨形态发生蛋白/信号转导分子和转录激活因子信号之间的相互作用抑制骨形态发生蛋白-2诱导的成骨细胞分化。
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CX43 change in LPS preconditioning against apoptosis of mesenchymal stem cells induced by hypoxia and serum deprivation is associated with ERK signaling pathway.
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Mol Cell Biochem. 2013 Aug;380(1-2):267-75. doi: 10.1007/s11010-013-1683-x. Epub 2013 May 28.