Reduced collagen deposition in infarcted myocardium facilitates induced pluripotent stem cell engraftment and angiomyogenesis for improvement of left ventricular function.
Reduced collagen deposition in infarcted myocardium facilitates induced pluripotent stem cell engraftment and angiomyogenesis for improvement of left ventricular function.
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DOI：
10.1016/j.jacc.2011.06.062
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发表时间：
2011-11-08
影响因子：
24
通讯作者：
Wang, Yigang
中科院分区：
文献类型：
--
作者：
Dai, Bo;Huang, Wei;Xu, Meifeng;Millard, Ronald W.;Gao, Mei Hua;Hammond, H. Kirk;Menick, Donald R.;Ashraf, Muhammad;Wang, Yigang
关键词：
本研究旨在评估瘢痕组织成分对祖细胞植入梗死心肌的影响。
心肌梗死后瘢痕组织的形成造成了一道屏障，严重阻碍了组织再生，限制了潜在的功能恢复。
体外实验：用诱导多能干细胞衍生的心肌细胞、内皮细胞和小鼠胚胎成纤维细胞接种并培养腹膜，制成三细胞补片（Tri - P）。通过蛋白质印迹法和定量逆转录聚合酶链反应测量小鼠胚胎成纤维细胞和梗死心脏中纤维化相关分子的表达。体内实验：在过表达腺苷酸环化酶6（AC6）的小鼠心肌梗死7天后，将Tri - P固定在整个梗死区域。通过体内生物发光成像、死后体外组织分析以及绿色荧光蛋白阳性细胞数量相结合的方法，比较AC6小鼠心脏中祖细胞的植入效率与对照野生型（WT）小鼠的情况。每周进行左心室（LV）功能的超声心动图检查。在应用Tri - P 4周后获取心脏进行分析。在缺氧/复氧实验前用毛喉素刺激小鼠胚胎成纤维细胞，并分析纤维化相关分子。
在AC6小鼠中，经Tri - P治疗的梗死心脏比WT小鼠显示出明显更高的生物发光成像强度和绿色荧光蛋白阳性细胞数量。从第2周到第4周，AC6小鼠的LV功能逐渐改善，且与LV纤维化减轻相关。
在AC6小鼠中应用Tri - P导致诱导多能干细胞植入显著增加，同时梗死区域出现血管心肌生成，LV功能得到改善。
The purpose of this study was to assess the effect of scar tissue composition on engraftment of progenitor cells into infarcted myocardium. Scar tissue formation after myocardial infarction creates a barrier that severely compromises tissue regeneration, limiting potential functional recovery. In vitro: A tricell patch (Tri-P) was created from peritoneum seeded and cultured with induced pluripotent stem cell–derived cardiomyocytes, endothelial cells, and mouse embryonic fibroblasts. The expression of fibrosis-related molecules from mouse embryonic fibroblasts and infarcted heart was measured by Western blot and quantitative reverse transcriptase polymerase chain reaction. In vivo: A Tri-P was affixed over the entire infarcted area 7 days after myocardial infarction in mice overexpressing adenylyl cyclase 6 (AC6). Engraftment efficiency of progenitor cells in hearts of AC6 mice was compared with that of control wild-type (WT) mice using a combination of in vivo bioluminescence imaging, post-mortem ex vivo tissue analysis, and the number of green fluorescent protein–positive cells. Echocardiography of left ventricular (LV) function was performed weekly. Hearts were harvested for analysis 4 weeks after Tri-P application. Mouse embryonic fibroblasts were stimulated with forskolin before an anoxia/reoxygenation protocol. Fibrosis-related molecules were analyzed. In AC6 mice, infarcted hearts treated with Tri-P showed significantly higher bioluminescence imaging intensity and numbers of green fluorescent protein–positive cells than in WT mice. LV function improved progressively in AC6 mice from weeks 2 to 4 and was associated with reduced LV fibrosis. Application of a Tri-P in AC6 mice resulted in significantly higher induced pluripotent stem cell engraftment accompanied by angiomyogenesis in the infarcted area and improvement in LV function.
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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
影响因子：
64.8
作者：
Srivastava, D;Ivey, KN
通讯作者：
Ivey, KN
影响因子：
37.8
作者：
Tang, Tong;Gao, Mei Hua;Hammond, H. Kirk
通讯作者：
Hammond, H. Kirk
影响因子：
6
作者：
Liao, Song-Yan;Siu, Chung-Wah;Tse, Hung-Fat
通讯作者：
Tse, Hung-Fat
影响因子：
3.3
作者：
Maeda, Masanori;Yamato, Masayuki;Okano, Teruo
通讯作者：
Okano, Teruo