Bcl-2 Expression Enhances Myoblast Sheet Transplantation Therapy for Acute Myocardial Infarction
Bcl-2 Expression Enhances Myoblast Sheet Transplantation Therapy for Acute Myocardial Infarction
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DOI：
10.3727/096368909x486048
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发表时间：
2010-01-01
影响因子：
3.3
通讯作者：
Harjula, Ari
中科院分区：
文献类型：
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作者：
Kitabayashi, Katsukiyo;Siltanen, Antti;Harjula, Ari
成肌细胞片移植是治疗缺血性心力衰竭的一种有前途的新方法。然而，低的血液和营养供应可能会危及床单的生存。本研究的目的是探讨Bcl-2修饰的成肌细胞在细胞片移植治疗中的作用。在表达Bcl-2的大鼠L 6成肌细胞片（L 6-Bcl 2）中，与野生型（L 6-WT）片相比，肌细胞标志物和血管生成介质的表达明显增加。L 6-Bcl 2片层表现出对凋亡刺激的显著抗性，并且其体外分化能力增加。我们评估了Bcl-2修饰的成肌细胞片在大鼠急性心肌梗死（AMI）模型中的治疗效果。64只Wistar大鼠分为4组。一组接受AMI（n = 22），另一组接受AMI和L 6-WT片移植（n = 17），第三组接受AMI和L 6-Bcl 2片移植（n = 20）。5只大鼠进行假手术。在3、10和28天后进行超声心动图检查。在研究结束时收集用于组织学分析的样品。AMI后，Bcl-2表达片在梗死心肌上存活更长时间，并显著改善心功能。L 6-Bcl 2片移植可减少心肌纤维化，增加梗死区和边缘区的血管密度。L 6-Bcl 2组心肌中c-kit阳性细胞和增殖细胞数量增加。总之，Bcl-2抑制成肌细胞片的存活，增加促血管生成旁分泌介质的产生，并增强细胞片移植的治疗效果。
Myoblast sheet transplantation is a promising novel treatment modality for heart failure after an ischemic insult. However, low supply of blood and nutrients may compromise sheet survival. The aim of this study was to investigate the effect of mitochondria-protective Bcl-2-modified myoblasts in cell sheet transplantation therapy. In the Bcl-2-expressing rat L6 myoblast sheets (L6-Bcl2), increased expression of myocyte markers and angiogenic mediators was evident compared to wild-type (L6-WT) sheets. The L6-Bcl2 sheets demonstrated significant resistance to apoptotic stimuli, and their differentiation capacity in vitro was increased. We evaluated the therapeutic effect of Bcl-2-modified myoblast sheets in a rat model of acute myocardial infarction (AMI). Sixty-four Wistar rats were divided into four groups. One group underwent AMI (n = 22), another AMI and L6-WT sheet transplantation (it = 17), and a third AMI and L6-Bcl2 sheet transplantation (n = 20). Five rats underwent a sham operation. Echocardiography was performed after 3, 10, and 28 days. Samples for histological analysis were collected at the end of the study. After AMI, the Bcl-2-expressing sheets survived longer on the infarcted myocardium, and significantly improved cardiac function. L6-Bcl2 sheet transplantation reduced myocardial fibrosis and increased vascular density in infarct and border areas. Moreover, the number of c-kit-positive and proliferating cells in the myocardium was increased in the L6-Bcl2 group. In conclusion, Bcl-2 prolongs survival of myoblast sheets, increases production of proangiogenic paracrine mediators, and enhances the therapeutic efficacy of cell sheet transplantation.