Circ Res：受损心脏细胞再生的基因“开关”

近日，研究人员使用microRNA已经能将疤痕组织转换成再生的心脏肌肉，相关研究论文发表在<em>Circulation Research</em>杂志上。
<div id="ztload"> 心脏病发作后，心脏肌肉不容易再生，成纤维细胞的疤痕组织会积累，增加心脏衰竭的风险。
研究人员已经尝试了各种方法包括利用干细胞来再生受损的心脏肌肉组织，达勒姆市杜克大学医学中心的医学教授Victor J. Dzau医师表示：这是第一次使用microRNA将成纤维细胞重编进入心脏肌肉内。我们不仅证实细胞培养方法能再生组织，同时也在老鼠身上得到验证。</div>
<!--more-->Dzau说：使用microRNA比许多组织再生的其他方法更简单。他说例如干细胞不太容易开张研究工作，因为这涉及到伦理问题。 这项研究克服干细胞再生医学研究遇到的困难，可用于组织损伤如中风和脊髓损伤等疾病。

研究团队确定了成纤维细胞转换成肌肉细胞的三个microRNA类型组合。研究人员下一步将研究关注于是否microRNA修复较大动物的受损的心脏，并改善心脏功能。如果这些研究证明安全有效，他们将开始人体研究。Dzau说：“如果一切实现，我认为我们将在未来十年看到该技术的治疗效果”。
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<br/><strong>文献链接</strong><br/>


<br/><strong><a href="http://circres.ahajournals.org/content/early/2012/04/26/CIRCRESAHA.112.269035">http://circres.ahajournals.org/content/early/2012/04/26/CIRCRESAHA.112.269035</a></strong><br/>


<br/><strong>MicroRNA-Mediated In Vitro and In Vivo Direct Reprogramming of Cardiac Fibroblasts to Cardiomyocytes
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Tilanthi M. Jayawardena, Bakytbek Egemnazarov, Elizabeth A. Finch, Lunan Zhang, J. Alan Payne, Kumar Pandya, et al.
<p id="p-1"><br/><strong><em>Rationale:</em></strong><br/>
Repopulation of the injured heart with new, functional cardiomyocytes remains a daunting challenge for cardiac regenerative medicine. An ideal therapeutic approach would involve an effective method at achieving direct conversion of injured areas to functional tissue in situ.</p>

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<p id="p-2"><br/><strong><em>Objective:</em></strong><br/>
The aim of this study was to develop a strategy that identified and evaluated the potential of specific micro (mi)RNAs capable of inducing reprogramming of cardiac fibroblasts directly to cardiomyocytes in vitro and in vivo.</p>

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<p id="p-3"><br/><strong><em>Methods and Results:</em></strong><br/>
Using a combinatorial strategy, we identified a combination of miRNAs 1, 133, 208, and 499 capable of inducing direct cellular reprogramming of fibroblasts to cardiomyocyte-like cells in vitro. Detailed studies of the reprogrammed cells demonstrated that a single transient transfection of the miRNAs can direct a switch in cell fate as documented by expression of mature cardiomyocyte markers, sarcomeric organization, and exhibition of spontaneous calcium flux characteristic of a cardiomyocyte-like phenotype. Interestingly, we also found that miRNA-mediated reprogramming was enhanced 10-fold on JAK inhibitor I treatment. Importantly, administration of miRNAs into ischemic mouse myocardium resulted in evidence of direct conversion of cardiac fibroblasts to cardiomyocytes in situ. Genetic tracing analysis using Fsp1Cre-traced fibroblasts from both cardiac and noncardiac cell sources strongly suggests that induced cells are most likely of fibroblastic origin.</p>

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<p id="p-4"><br/><strong><em>Conclusions:</em></strong><br/>
The findings from this study provide proof-of-concept that miRNAs have the capability of directly converting fibroblasts to a cardiomyocyte-like phenotype in vitro. Also of significance is that this is the first report of direct cardiac reprogramming in vivo. Our approach may have broad and important implications for therapeutic tissue regeneration in general.</p>

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