Cardiosphere-Derived Cells Facilitate Heart Repair by Modulating M1/M2 Macrophage Polarization and Neutrophil Recruitment.
Cardiosphere-Derived Cells Facilitate Heart Repair by Modulating M1/M2 Macrophage Polarization and Neutrophil Recruitment.
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DOI：
10.1371/journal.pone.0165255
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Li TS
中科院分区：
文献类型：
--
作者：
Hasan AS;Luo L;Yan C;Zhang TX;Urata Y;Goto S;Mangoura SA;Abdel-Raheem MH;Zhang S;Li TS
心肌球源性细胞（CDC）是心肌修复的有前途的干细胞来源之一，已在临床试验中进行了测试并产生了有益的效果;然而，相关机制尚未完全了解。在这项研究中，我们研究了CDCs通过将巨噬细胞从促炎表型（M1）转换为调节性抗炎表型（M2）来促进心脏修复的假设。将小鼠巨噬细胞与CDC条件培养基或成纤维细胞条件培养基培养作为对照。免疫组化结果显示，培养3 d后，CDCs条件培养液显著增强了M2巨噬细胞标志物CD 206的表达，但降低了M1巨噬细胞标志物CD 86的表达。对于动物研究，我们使用小鼠急性心肌梗死模型。我们将CDC、成纤维细胞或生理盐水仅注射到梗死边缘区。分别于给药后第5天和第14天采集心脏组织进行组织学分析。与对照组相比，CDCs治疗显著减少了M1巨噬细胞和中性粒细胞，但增加了M2巨噬细胞在梗死心脏。此外，与对照组相比，CDC治疗的小鼠具有减少的梗死面积和更少的凋亡细胞。我们的数据表明，CDCs通过调节M1/M2巨噬细胞极化和中性粒细胞募集促进心脏修复，这可能为基于干细胞的心肌修复机制提供新的见解。
Cardiosphere-derived cells (CDCs), one of the promising stem cell sources for myocardial repair, have been tested in clinical trials and resulted in beneficial effects; however, the relevant mechanisms are not fully understood. In this study, we examined the hypothesis that CDCs favor heart repair by switching the macrophages from a pro-inflammatory phenotype (M1) into a regulatory anti-inflammatory phenotype (M2). Macrophages from mice were cultured with CDCs-conditioned medium or with fibroblasts-conditioned medium as a control. Immunostaining showed that CDCs-conditioned medium significantly enhanced the expression of CD206 (a marker for M2 macrophages), but decreased the expression of CD86 (a marker for M1 macrophages) 3 days after culture. For animal studies, we used an acute myocardial infarction model of mice. We injected CDCs, fibroblasts, or saline only into the border zone of infarction. Then we collected the heart tissues for histological analysis 5 and 14 days after treatment. Compared with control animals, CDCs treatment significantly decreased M1 macrophages and neutrophils but increased M2 macrophages in the infarcted heart. Furthermore, CDCs-treated mice had reduced infarct size and fewer apoptotic cells compared to the controls. Our data suggest that CDCs facilitate heart repair by modulating M1/M2 macrophage polarization and neutrophil recruitment, which may provide a new insight into the mechanisms of stem cell-based myocardial repair.
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影响因子：
168.9
作者：
Makkar, Raj R.;Smith, Rachel R.;Cheng, Ke;Malliaras, Konstantinos;Thomson, Louise E. J.;Berman, Daniel;Czer, Lawrence S. C.;Marban, Linda;Mendizabal, Adam;Johnston, Peter V.;Russell, Stuart D.;Schuleri, Karl H.;Lardo, Albert C.;Gerstenblith, Gary;Marban, Eduardo
通讯作者：
Marban, Eduardo
影响因子：
2.6
作者：
Kim, Jaehyup;Hematti, Peiman
通讯作者：
Hematti, Peiman
影响因子：
5.2
作者：
Li, Tao-Sheng;Cheng, Ke;Lee, Shuo-Tsan;Matsushita, Satoshi;Davis, Darryl;Malliaras, Konstantinos;Zhang, Yiqiang;Matsushita, Noriko;Smith, Rachel Ruckdeschel;Marban, Eduardo
通讯作者：
Marban, Eduardo
影响因子：
39.3
作者：
Aminzadeh, Mohammad A.;Tseliou, Eleni;Marban, Eduardo
通讯作者：
Marban, Eduardo
影响因子：
12.4
作者：
Francois, Moira;Romieu-Mourez, Raphaelle;Galipeau, Jacques
通讯作者：
Galipeau, Jacques