Cardiosphere-derived cell sheet primed with hypoxia improves left ventricular function of chronically infarcted heart.
Cardiosphere-derived cell sheet primed with hypoxia improves left ventricular function of chronically infarcted heart.
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发表时间：
2015-12
影响因子：
2.2
通讯作者：
Tohru Hosoyama;M. Samura;T. Kudo;Arata Nishimoto;Koji Ueno;Tomoaki Murata;T. Ohama;Koichi Sato;A. Mikamo;K. Yoshimura;Tao-Sheng Li;K. Hamano
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文献类型：
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作者：
Tohru Hosoyama;M. Samura;T. Kudo;Arata Nishimoto;Koji Ueno;Tomoaki Murata;T. Ohama;Koichi Sato;A. Mikamo;K. Yoshimura;Tao-Sheng Li;K. Hamano
从出生后心脏组织中分离的心肌球源性细胞（CDCs）是治疗心肌梗死的一种方便有效的资源。然而，CDC在梗死心脏中的不良保留通常导致不太理想的治疗结果。细胞片层技术已被开发为允许移植细胞更长时间保留的手段，并且这种治疗策略为严重缺血性疾病的基于细胞的治疗开辟了新的途径。然而，在这种治疗方法可以在临床环境中常规应用之前，仍有改进的余地。在这项研究中，我们调查是否缺氧预处理提高CDC单层片的治疗效果。为了诱导缺氧引发，将CDC单层片置于调节至2%氧气的培养箱中24小时，然后将预处理的小鼠CDC片植入陈旧心肌梗死小鼠模型的梗死心脏中。CDC片的低氧预处理通过PI 3-kinase/Akt信号通路显著增加血管内皮生长因子的表达。植入预处理的CDC片可改善慢性梗死心脏的左室功能，减少纤维化。预处理的CDC片的治疗效果高于常氧条件下培养的CDC片。这些结果表明，低氧预处理增强CDC片的治疗性血管生成和抗纤维化活性。细胞片和低氧预处理的组合为CDC移植到慢性梗死心脏中提供了一种有吸引力的治疗方案。
Cardiosphere-derived cells (CDCs) isolated from postnatal heart tissue are a convenient and efficientresource for the treatment of myocardial infarction. However, poor retention of CDCs in infarcted hearts often causes less than ideal therapeutic outcomes. Cell sheet technology has been developed as a means of permitting longer retention of graft cells, and this therapeutic strategy has opened new avenues of cell-based therapy for severe ischemic diseases. However, there is still scope for improvement before this treatment can be routinely applied in clinical settings. In this study, we investigated whether hypoxic preconditioning enhances the therapeutic efficacy of CDC monolayer sheets. To induce hypoxia priming, CDC monolayer sheets were placed in an incubator adjusted to 2% oxygen for 24 hours, and then preconditioned mouse CDC sheets were implanted into the infarcted heart of old myocardial infarction mouse models. Hypoxic preconditioning of CDC sheets remarkably increased the expression of vascular endothelial growth factor through the PI3-kinase/Akt signaling pathway. Implantation of preconditioned CDC sheets improved left ventricular function inchronically infarcted hearts and reduced fibrosis. The therapeutic efficacy of preconditioned CDC sheets was higher than the CDC sheets that were cultured under normaxia condition. These results suggest that hypoxic preconditioning augments the therapeutic angiogenic and anti-fibrotic activity of CDC sheets. A combination of cell sheets and hypoxic preconditioning offers an attractive therapeutic protocol for CDC transplantation into chronically infarcted hearts.