近日,，研究人員使用microRNA已經(jīng)能將疤痕組織轉(zhuǎn)換成再生的心臟肌肉,，相關(guān)研究論文發(fā)表在Circulation Research雜志上,。
心臟病發(fā)作后,，心臟肌肉不容易再生,，成纖維細胞的疤痕組織會積累,，增加心臟衰竭的風(fēng)險,。
研究人員已經(jīng)嘗試了各種方法包括利用干細胞來再生受損的心臟肌肉組織，達勒姆市杜克大學(xué)醫(yī)學(xué)中心的醫(yī)學(xué)教授Victor J. Dzau醫(yī)師表示：這是第一次使用microRNA將成纖維細胞重編進入心臟肌肉內(nèi),。我們不僅證實細胞培養(yǎng)方法能再生組織,，同時也在老鼠身上得到驗證。
Dzau說：使用microRNA比許多組織再生的其他方法更簡單,。他說例如干細胞不太容易開張研究工作,，因為這涉及到倫理問題,。 這項研究克服干細胞再生醫(yī)學(xué)研究遇到的困難，可用于組織損傷如中風(fēng)和脊髓損傷等疾病,。
研究團隊確定了成纖維細胞轉(zhuǎn)換成肌肉細胞的三個microRNA類型組合,。研究人員下一步將研究關(guān)注于是否microRNA修復(fù)較大動物的受損的心臟，并改善心臟功能,。如果這些研究證明安全有效,，他們將開始人體研究。Dzau說：“如果一切實現(xiàn),，我認為我們將在未來十年看到該技術(shù)的治療效果”,。（生物谷：Bioon.com）
doi:10.1161/CIRCRESAHA.112.269035
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MicroRNA-Mediated In Vitro and In Vivo Direct Reprogramming of Cardiac Fibroblasts to Cardiomyocytes
Tilanthi M. Jayawardena, Bakytbek Egemnazarov, Elizabeth A. Finch, Lunan Zhang, J. Alan Payne, Kumar Pandya, et al.
Rationale: 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.
Objective: 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.
Methods and Results: 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.
Conclusions: 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.
