Mobilized bone marrow progenitor cells serve as donors of cytoprotective genes for cardiac repair
Mobilized bone marrow progenitor cells serve as donors of cytoprotective genes for cardiac repair
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DOI：
10.1016/j.yjmcc.2007.11.011
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发表时间：
2008-03-01
影响因子：
5
通讯作者：
Xu, Meifeng
中科院分区：
文献类型：
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作者：
Dai, Ying;Ashraf, Muhammad;Xu, Meifeng
我们在这里提出，从骨髓动员祖细胞（MPC）是特殊的细胞类型，携带细胞保护蛋白的心脏缺血后修复。结扎小鼠冠状动脉左前降支（LAD）造成心肌缺血。通过荧光激活细胞分选（FACS）分析外周血中的祖细胞。通过ELISA、RT-PCR和/或实时定量PCR检测细胞保护基因的表达。G-CSF在缺血心肌中表达明显上调。在LAD结扎后，血清G-CSF和循环中的祖细胞之间观察到良好的相关性。除了表达骨髓干细胞（BMSCs）的表面标志物外，MPCs还过表达心脏转录因子加塔-4和抗凋亡因子Bcl-2。将培养的MPCs移植到缺血边缘区可通过缩小梗死面积显著改善心功能。更重要的是，当与心肌细胞共培养时，MPC显著地保护心肌细胞免于凋亡。MPCs的心肌保护作用可被Bcl-2中和抗体和加塔-4 siRNA阻断。相比之下，用加塔-4转染骨髓间充质干细胞可增强对心肌细胞抗凋亡的保护作用。它的结论是，MPC是高度的细胞保护和携带保护基因负责心脏修复。(C)2007年爱思唯尔公司All rights reserved.
We proposed here that mobilized progenitor cells (MPCs) from the bone marrow are special cell types which carry cytoprotective proteins for cardiac repair following ischemia. Myocardial ischemia was induced by ligation of the left anterior descending coronary artery (LAD) in mice. Progenitor cells in peripheral blood were analyzed by fluorescence-activated cell sorting (FACS). The expression of cytoprotective genes was assayed by ELISA, RT-PCR, and/or real-time PCR. G-CSF was markedly up-regulated in the ischemic myocardium. A good correlation was observed between serum G-CSF and progenitor cells in circulation following LAD ligation. MPCs overexpressed cardiac transcription factor, GATA-4, and anti-apoptotic factor, Bcl-2, besides expression of the surface markers of bone marrow stem cells (BMSCs). Transplantation of cultured MPCs into the ischetmic border area significantly improved cardiac function by reducing infarction size. More importantly, MPCs significantly protected cardiomyocytes against apoptosis when co-cultured with cardiomyocytes. The cardiac protection by MPCs was blocked by Bcl-2 neutralizing antibody and GATA-4 siRNA. In contrast, transfection of BMSCs with GATA-4 provided increased protection of myocytes against apoptosis. It is concluded that MPCs are highly cytoprotective and carry protective genes responsible for cardiac repair. (C) 2007 Elsevier Inc. All rights reserved.