Nature：美科学家发现心脏修复的新策略

5月13日，Nature在线发表了德克萨斯大学西南医学中心等多家科研单位的一篇题为Heart repair by reprogramming non-myocytes with cardiac transcription factors的文章，研究表明：在体内或体外通过四种心脏转录因子（GATA4，HAND2， MEF2C and TBX5）可以将成年鼠纤维原细胞重编程为功能性的心脏样肌细胞。

心肌细胞的功能异常或丧失是心脏病患者的根本死因，然而成年哺乳动物的心脏修复能力是有限的。心脏再生医学的根本目的是通过更换心肌细胞和降低纤维化来成功地修复心脏。心脏干细胞的移植来提高心脏功能在临床上具有可能性，但是效率相对太低。

纤维原细胞通过不同的转录因子的组合可以重编程为多能干细胞、肌肉细胞和神经元。人的心脏中包含有大约30%的心肌细胞和60%-70%的心脏纤维原细胞。

这项研究成果为心脏修复开辟了新的道路。

doi：10.1038/nature11139
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PMID:

Heart repair by reprogramming non-myocytes with cardiac transcription factors

Kunhua Song，  Young-Jae Nam，  Xiang Luo，  Xiaoxia Qi，  Wei Tan，  Guo N. Huang，  Asha Acharya， Christopher L. Smith，  Michelle D. Tallquist，  Eric G. Neilson，  Joseph A. Hill，  Rhonda Bassel-Duby  & Eric N. Olson

Abstract

The adult mammalian heart possesses little regenerative potential following injury. Fibrosis due to activation of cardiac fibroblasts impedes cardiac regeneration and contributes to loss of contractile function， pathological remodelling and susceptibility to arrhythmias. Cardiac fibroblasts account for a majority of cells in the heart and represent a potential cellular source for restoration of cardiac function following injury through phenotypic reprogramming to a myocardial cell fate. Here we show that four transcription factors， GATA4， HAND2， MEF2C and TBX5， can cooperatively reprogram adult mouse tail-tip and cardiac fibroblasts into beating cardiac-like myocytes in vitro. Forced expression of these factors in dividing non-cardiomyocytes in mice reprograms these cells into functional cardiac-like myocytes， improves cardiac function and reduces adverse ventricular remodelling following myocardial infarction. Our results suggest a strategy for cardiac repair through reprogramming fibroblasts resident in the heart with cardiogenic transcription factors or other molecules.