Gene Therapy Improves Heart Regeneration
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Ways to spur greater regeneration following major organ failures that occur in aging are an improvement over the present situation, but better healing of the consequences of a high-mortality event after the fact is nowhere near as good as preventing that event from occurring in the first place. Some of the approaches that spur greater healing may indeed help in that regard, if delivered up front to boost organ maintenance by stem cells, or via similar mechanisms, but the best option is to revert the low-level cellular and molecular damage that causes systemic organ failure.

Here researchers show that via gene therapy it is possible to spur greater cellular activity and regeneration in pig hearts following heart attack:

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.

Link: http://dx.doi.org/10.1126/scitranslmed.3007668

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