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Sci. Transl. Med:用基因疗法令心肌再生

  1. Sci. Transl. Med
  2. 基因疗法
  3. 心肌再生

来源:EurekAlert! 2014-02-21 14:16

据一项新的研究报道,基因疗法可帮助猪体内的心肌再生。CCNA2是一个指示胚胎心脏细胞分裂和生长的基因。因为在动物和人出生后这一胚胎基因通路会进入休眠状态,因此成年心肌细胞无法迅速而容易地应对像心肌梗塞这样的损伤而进行分裂。细胞分裂对组织再生是至关重要的(这可以解释为什么皮肤及其它器官会在损伤后愈合而心脏则不能)。

据一项新的研究报道,基因疗法可帮助猪体内的心肌再生。CCNA2是一个指示胚胎心脏细胞分裂和生长的基因。因为在动物和人出生后这一胚胎基因通路会进入休眠状态,因此成年心肌细胞无法迅速而容易地应对像心肌梗塞这样的损伤而进行分裂。细胞分裂对组织再生是至关重要的(这可以解释为什么皮肤及其它器官会在损伤后愈合而心脏则不能)。

Hina Chaudhry与Scott Shapiro及其同事将CCNA2基因注射到刚发生了心肌梗塞之后的猪心内。这些经过处理的心脏组织不但能再生,而且研究人员看到了在心肌梗塞区域的周围有出现新的心肌细胞的迹象以及心脏泵血功能的显著改善。这些发现提示,在心肌梗塞后采取基因疗法可帮助强化病人的心脏。

文章的作者现在正在猪的体内进行基因输送系统的研究,这种输送系统被设计成与人体更为兼容。((生物谷Bioon.com)

生物谷推荐的英文摘要:

Sci. Transl. Med.    DOI: 10.1126/scitranslmed.3007668

Cyclin A2 Induces Cardiac Regeneration After Myocardial Infarction Through Cytokinesis of Adult Cardiomyocytes

Scott D. Shapiro1,*,?, Amaresh K. Ranjan1,*, Yoshiaki Kawase1, Richard K. Cheng2, Rina J. Kara1, Romit Bhattacharya1, Gabriela Guzman-Martinez1,?, Javier Sanz1, Mario J. Garcia1,§ and Hina W. Chaudhry1,?

Cyclin A2 (Ccna2), normally silenced after birth in the mammalian heart, can induce cardiac repair in small-animal models of myocardial infarction. We report that delivery of the Ccna2 gene to infarcted porcine hearts invokes a regenerative response. We used a catheter-based approach to occlude the left anterior descending artery in swine, which resulted in substantial myocardial infarction. A week later, we performed left lateral thoracotomy and injected adenovirus carrying complementary DNA encoding CCNA2 or null adenovirus into peri-infarct myocardium. Six weeks after treatment, we assessed cardiac contractile function using multimodality imaging including magnetic resonance imaging, which demonstrated ~18% increase in ejection fraction of Ccna2-treated pigs and ~4% decrease in control pigs. Histologic studies demonstrate in vivo evidence of increased cardiomyocyte mitoses, increased cardiomyocyte number, and decreased fibrosis in the experimental pigs. Using time-lapse microscopic imaging of cultured adult porcine cardiomyocytes, we also show that Ccna2 elicits cytokinesis of adult porcine cardiomyocytes with preservation of sarcomeric structure. These data provide a compelling framework for the design and development of cardiac regenerative therapies based on cardiomyocyte cell cycle regulation.

 

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