Layered implantation of myoblast sheets attenuates adverse cardiac remodeling of the infarcted heart
Layered implantation of myoblast sheets attenuates adverse cardiac remodeling of the infarcted heart
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DOI：
10.1016/j.jtcvs.2009.02.004
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发表时间：
2009-10-01
影响因子：
6
通讯作者：
Sawa, Yoshiki
中科院分区：
文献类型：
--
作者：
Sekiya, Naosumi;Matsumiya, Goro;Sawa, Yoshiki
目的：我们以前的研究表明，用组织工程技术构建的自体成肌细胞片可以改善受损心脏的功能。在这项研究中，我们评估了分层成肌细胞片的影响，以澄清是否增加的数量提供了改善的心脏functions.Methods：成肌细胞片构建在培养皿中，通过温度降低释放融合细胞从培养皿表面。将60只刘易斯大鼠梗死区植入成肌细胞片。分为4组（每组n = 15）：S1：1层，S3：3层，S5：5层，假手术组。我们通过超声心动图和心导管检查心功能，通过真实的时间逆转录聚合酶链反应检测mRNA表达，并进行组织学检查。结果：S5和S3组的射血分数和收缩末期压力-容积关系显著改善。S5组舒张末期面积显著减小。肝细胞生长因子、血管内皮生长因子和基质细胞衍生因子-1的mRNA均以剂量依赖性方式上调。在组织学检查中，纤维化在S5中减少最多，血管密度增加。S5和S3组的细胞肥大均减弱。弹性纤维被大量上调的梗死和植入片中的S5和S3组，与弹性蛋白gene. Conclusions的表达：植入的三层和五层成肌细胞片产生有利的结果，更好地改善心脏功能，诱导血管生成，更多的弹性纤维，和更少的纤维化。因此，分层成肌细胞片，在最佳数量，可能会减弱不利的心脏重构的梗死心脏。
Objective: We previously showed that autologous myoblast sheets constructed with tissue-engineering techniques improved the function of the impaired heart. In this study, we evaluated the effects of layered myoblast sheets to clarify whether increasing the number of sheets provides improvement of cardiac function.Methods: Myoblast sheets were constructed in dishes that release confluent cells from the dish surface via temperature reduction. Sixty infarcted Lewis rats underwent implantation of myoblast sheets on the infarcted area. There were 4 groups (n = 15 in each group): S1: one layer, S3: three layers, S5: five layers, and a sham group. We examined cardiac function by echocardiography and catheterization, mRNA expression by real time reverse-transcriptase polymerase chain reaction, and histology.Results: The ejection fraction and end-systolic pressure-volume relationship in the S5 and S3 groups were significantly improved. End-diastolic area was significantly reduced in the S5 group. The mRNAs for hepatocyte growth factor, vascular endothelial growth factor, and stromal cell-derived factor-1 were all up-regulated in dose-dependent fashion. On histologic examination, fibrosis was most decreased in S5, and vascular density was increased. Cellular hypertrophy was attenuated in both the S5 and S3 groups. Elastic fibers were massively up-regulated in the infarction and implanted sheets in the S5 and S3 groups, with expression of the elastin gene.Conclusions: Implantation of three-and five-layered myoblast sheets yields favorable results, with better improvement of cardiac function, induction of angiogenesis, more elastic fibers, and less fibrosis. Thus, layered myoblast sheets, in optimal numbers, may attenuate adverse cardiac remodeling of the infarcted heart.