I-Corps: Regeneration of Cardiac Muscle

这个i-Corps项目的更广泛的影响/商业潜力是，它承诺改善与心脏病发作或其他心脏病引起的人类心力衰竭相关的结果。这将通过使用心脏诱导核糖核酸(CIR)将给定患者的皮肤细胞转化为心肌来实现。患者心脏的疤痕/受损组织可能会被心肌取代。目前，治疗心力衰竭的典型选择是全心脏移植。这项新技术将使用微创技术，经过CIR处理的细胞将被注射到受损的心脏中，使用与冠状动脉血管成形术类似的技术。美国每年有85万人死于心脏病，全球每年有1800万人死于心脏病。这些人中的许多人可能会通过使用CIR进行治疗。这项尖端技术还有可能为其他重要器官的再生提供新的方法。I-Corps项目进一步发现了人类心脏中的心脏诱导RNA(CIR)，它具有将非肌肉细胞转化为心肌的能力。已有研究表明，这种人类来源的CIR能够促进正常心肌未分化的隐性心脏突变无功能胚胎轴的心肌形成。进一步的研究发现，人来源的CIR在体外也能诱导多能干细胞(IPSCs)和成纤维细胞分化为特定的心肌细胞。CIR处理的细胞在体外显示出特有的心梭形状，并表达心肌蛋白并形成有组织的肌原纤维。下一步将是利用CIR转基因的IPSCs和成纤维细胞进行体内研究，以修复/再生心肌梗死动物模型中受损的心肌组织。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is that it promises to improve outcomes related to heart failure in humans that result from heart attacks or other heart diseases. This would be accomplished by converting skin cells from a given patient into cardiac muscle by using a cardiac inducing ribonucleic acid (CIR). The scar/damaged tissues of the patient's heart would be potentially be replaced with cardiac muscle. Currently, the typicaly option for curing heart failure is total heart transplantation. This new technology would use minimally invasive techniques with CIR treated cells would be injected into the damaged heart using techniques similar to those used for coronary angioplasty. Heart diseases cause 850,000 deaths per year in the USA and 18 million globally. Many of these people could potentially be treated by using CIR. This cutting edge technology has the potential also to enable new approaches for the regeneration of other vital organs.This I-Corps project further develops a discovery of a Cardiac Inducing RNA (CIR) in human heart that has the ability to convert non-muscle cells into cardiac muscle. It has been shown that this human-derived CIR has the ability to promote cardiac muscle formation in genetically recessive cardiac mutant non-function embryonic axolotl hearts where ordinarily cardiac muscle had not differentiated. In further studies it was found that the human-derived CIR also induced pluripotent stem cells (iPSCs) and fibroblasts into definitive cardiomyocytes in vitro when transfected into these cells using lipofectin vesicles. The CIR-treated cells showed characteristic cardiac spindle shapes in vitro and expressed cardiac proteins as well as formed organized myofibrils. The next steps will be to pursue in vivo studies using CIR-transfected iPSCs and fibroblasts to repair/regenerate damaged heart muscle tissues in animal models of myocardial infarction.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.