Tissue cardiomyoplasty using bioengineered contractile cardiomyocyte sheets to repair damaged myocardium: Their integration with recipient myocardium
Tissue cardiomyoplasty using bioengineered contractile cardiomyocyte sheets to repair damaged myocardium: Their integration with recipient myocardium
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DOI：
10.1097/01.tp.0000181163.69108.dd
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发表时间：
2005-12-15
期刊：
影响因子：
6.2
通讯作者：
Matsuda, H
中科院分区：
文献类型：
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作者：
Miyagawa, S;Sawa, Y;Matsuda, H
背景我们假设，没有支架的组织工程化收缩心肌细胞片将显示与受损心肌的组织学和电整合，导致梗死心肌的再生。将新生大鼠心肌细胞培养在聚（N-异丙基丙烯酰胺）接枝的聚苯乙烯培养皿上，并在20 ℃下分离为方形细胞片。将两个薄片堆叠以形成较厚的收缩性心脏薄片。在横截面上，堆叠的薄片看起来像均匀的心脏样组织。结扎大鼠左前降支（LAD）2周后，进行两种处理：1）心肌细胞片植入（T组，n = 10）和2）成纤维细胞片植入（F组，n = 10）。对照组（C组，n = 10）不加任何治疗。超声心动图显示，植入后2、4和8周，T组的心脏性能明显改善。心肌细胞片贴附于梗死心肌，显示血管生成，表达连接蛋白-43，并在心肌中表现为同质组织。电生理实验显示，在T组治疗的瘢痕区域有一个QRS波群，但在其他组中有两个峰，指示分支阻滞。此外，T组的受体心脏起搏阈值低于其他组。在缺血心肌模型中，心肌细胞片层与受损心肌整合并改善心脏功能。使用这种组织工程细胞片的技术正在将组织心肌成形术的有前途的概念引入再生医学领域。
Background. We hypothesized that tissue-engineered contractile cardiomyocyte sheets without a scaffold would show histological and electrical integration with impaired myocardium, leading to the regeneration of infarcted myocardium.Methods. Neonatal rat cardiomyocytes were cultured on Poly(N-isopropylacrylamide)-grafted polystyrene dishes and detached as a square cell sheet at 20 degrees C. Two sheets were stacked to make thicker contractile cardiac sheets. In cross-section, the stacked sheets looked like homogeneous heart-like tissue. Two weeks after rats were subjected to left anterior descending (LAD) ligation, two treatments were conducted: 1) cardiomyocyte sheet implantation (T group, n = 10), and 2) fibroblast sheet implantation (F group, n = 10). The control group underwent no additional treatment (C group, n = 10).Results. Echocardiography demonstrated that cardiac performance was significantly ameliorated in the T group 2, 4, and 8 weeks after implantation. The cardiomyocyte sheets became attached to the infarcted myocardium, showed angiogenesis, expressed connexin-43, and appeared as homogeneous tissue in the myocardium Electrophysiological experiments showed a QRS complex with one peak in the treated scar area in the T group, but two peaks, indicative of branch block, in that of the other groups. Furthermore, the threshold for pacing of the recipient heart was lower in the T group than in the other groups.Conclusions. Cardiomyocyte sheets integrated with the impaired myocardium and improved cardiac performance in a model of ischemic myocardium. Techniques using such tissue-engineered cell sheets are introducing the promising concept of tissue cardiomyoplasty to the field of regenerative medicine.