Molecular strategy to reduce in vivo collagen barrier promotes entry of NCX1 positive inducible pluripotent stem cells (iPSC(NCX¹⁺)) into ischemic (or injured) myocardium.
Molecular strategy to reduce in vivo collagen barrier promotes entry of NCX1 positive inducible pluripotent stem cells (iPSC(NCX¹⁺)) into ischemic (or injured) myocardium.
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DOI：
10.1371/journal.pone.0070023
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Huang W;Dai B;Wen Z;Millard RW;Yu XY;Luther K;Xu M;Zhao TC;Yang HT;Qi Z;Lasance K;Ashraf M;Wang Y
本研究的目的是评估胶原成分对梗死心肌内祖细胞植入的影响。我们以前报道过，当心脏中过度表达腺苷酸环化酶-6（AC 6）的胶原蛋白减少时，心外膜补片中干/祖细胞的心肌内渗透增强。在这项研究中，我们假设了一种替代策略，其中microRNA-29 b（miR-29 b）的过表达，抑制编码参与纤维化的心脏成纤维细胞蛋白的mRNA，将类似地促进祖细胞迁移到梗死大鼠心肌中。 体外试验：建立由心脏钠-钙交换器-1（NCX 1）阳性iPSC（iPSCNCX 1+）、内皮细胞（EC）和小鼠胚胎成纤维细胞（MEF）组成的三细胞贴片（Tri-P），共培养，并接种在分离的腹膜上。通过qPCR和Western blot分析心脏成纤维细胞（CFb）中纤维化相关基因的表达。体内：在产生缺血诱导的局部心肌梗死（MI）之前，向裸大鼠心脏施用模拟miRNA-29 b（miR-29 b）、miRNA-29 b抑制剂（Anti-29 b）或阴性模拟物（Ctrl）。7天后将Tri-P放置在梗死区域上。通过显微CT成像和免疫荧光染色分析血管肌生成。每周进行超声心动图检查。与对照组和抗29 b组相比，过表达miR-29 b的心脏中绿色荧光蛋白阳性（GFP+）细胞的数量、毛细血管密度和心脏功能显著增加。相反，在体外和体内用抗29 b下调miR-29 b诱导间质纤维化和心脏重塑。miR-29 b的过表达显著减少了MI后的瘢痕形成，并促进iPSCNCX 1+从细胞补丁渗透到梗死区域，导致MI后心脏功能的恢复。
The purpose of this study was to assess the effect of collagen composition on engraftment of progenitor cells within infarcted myocardium. We previously reported that intramyocardial penetration of stem/progenitor cells in epicardial patches was enhanced when collagen was reduced in hearts overexpressing adenylyl cyclase-6 (AC6). In this study we hypothesized an alternative strategy wherein overexpression of microRNA-29b (miR-29b), inhibiting mRNAs that encode cardiac fibroblast proteins involved in fibrosis, would similarly facilitate progenitor cell migration into infarcted rat myocardium. In vitro: A tri-cell patch (Tri-P) consisting of cardiac sodium-calcium exchanger-1 (NCX1) positive iPSC (iPSCNCX1+), endothelial cells (EC), and mouse embryonic fibroblasts (MEF) was created, co-cultured, and seeded on isolated peritoneum. The expression of fibrosis-related genes was analyzed in cardiac fibroblasts (CFb) by qPCR and Western blot. In vivo: Nude rat hearts were administered mimic miRNA-29b (miR-29b), miRNA-29b inhibitor (Anti-29b), or negative mimic (Ctrl) before creation of an ischemically induced regional myocardial infarction (MI). The Tri-P was placed over the infarcted region 7 days later. Angiomyogenesis was analyzed by micro-CT imaging and immunofluorescent staining. Echocardiography was performed weekly. The number of green fluorescent protein positive (GFP+) cells, capillary density, and heart function were significantly increased in hearts overexpressing miR-29b as compared with Ctrl and Anti-29b groups. Conversely, down-regulation of miR-29b with anti-29b in vitro and in vivo induced interstitial fibrosis and cardiac remodeling. Overexpression of miR-29b significantly reduced scar formation after MI and facilitated iPSCNCX1+ penetration from the cell patch into the infarcted area, resulting in restoration of heart function after MI.
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影响因子：
24
作者：
Dai, Bo;Huang, Wei;Xu, Meifeng;Millard, Ronald W.;Gao, Mei Hua;Hammond, H. Kirk;Menick, Donald R.;Ashraf, Muhammad;Wang, Yigang
通讯作者：
Wang, Yigang
影响因子：
5
作者：
Huang W;Zhang D;Millard RW;Wang T;Zhao T;Fan GC;Ashraf A;Xu M;Ashraf M;Wang Y
通讯作者：
Wang Y
DOI：
10.1073/pnas.92.17.7686
发表时间：
1995-08-15
影响因子：
11.1
作者：
DUDLEY, DT;PANG, L;SALTIEL, AR
通讯作者：
SALTIEL, AR
影响因子：
82.9
作者：
Kusano, KF;Pola, R;Losordo, DW
通讯作者：
Losordo, DW
影响因子：
5.2
作者：
Simpson, David;Liu, Hong;Dudley, Samuel C., Jr.
通讯作者：
Dudley, Samuel C., Jr.