I-Corps: Regeneration of Cardiac Muscle

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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.