Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling
Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling
复制标题
DOI：
10.1161/01.res.0000225952.61196.39
复制
发表时间：
2006-06-09
影响因子：
20.1
通讯作者：
Ashraf, Muhammad
中科院分区：
文献类型：
--
作者：
Uemura, Ryota;Xu, Meifeng;Ashraf, Muhammad
在这项研究中，我们假设骨髓干细胞(BMSCs)通过旁分泌效应来保护缺血心肌，这种旁分泌效应可以通过预适应进一步增强。在体外实验中，缺氧后BMSCs的Akt和eNOS等细胞存活因子显著增加。在小鼠冠状动脉结扎后的第二系列实验中，随机注入DMEM(G-1)、BMSCs(G-2)和预适应的BMSCs(G-3)。心肌梗死后4d，G-2、G-3组损伤心肌内可见骨髓间充质干细胞。G-3组梗死区心肌细胞凋亡数明显减少。心肌梗死后4周，G-3组左心室(LV)内径变小，LV射血分数增加。G-3组心肌梗死面积明显缩小。而GFP(+)心肌细胞在G-2和G-3梗死区内数量较少。综上所述，骨髓间充质干细胞在缺血状态下能分泌细胞存活因子，并能阻止梗死区附近心肌细胞的凋亡。骨髓间充质干细胞的预适应增强了它们的存活率和减轻左心室重构的能力，这部分归因于旁分泌效应。
In this study, we hypothesized that bone marrow stem cells (BMSCs) protect ischemic myocardium through paracrine effects that can be further augmented with preconditioning. In in vitro experiments, cell survival factors such as Akt and eNOS were significantly increased in BMSCs following anoxia. In the second series of experiments following coronary ligation in mice, left ventricles were randomly injected with the following: DMEM (G-1), BMSCs (G-2), and preconditioned BMSCs (G-3). Four days after myocardial infarction, BMSCs were observed within injured myocardium in G-2 and G-3. Apoptotic cardiomyocytes within periinfarct area were significantly reduced in G-3. Four weeks after myocardial infarction, smaller left ventricular (LV) dimension and increased LV ejection fraction were observed in G-3. Infarct area was significantly reduced in G-3. However, GFP(+) cardiomyocytes were observed in low numbers within periinfarct area in G-2 and G-3. In conclusion, BMSCs secreted cell survival factors under ischemia, and they prevented apoptosis in cardiomyocytes adjacent to the infarcted area. Preconditioning of BMSCs enhanced their survival and ability to attenuate LV remodeling, which was attributable, in part, to paracrine effects.