PFI-TT: Development of an enhanced molecular cargo via flow oscillations for heart regeneration

Award ID: 1941141

The broader impact/commercial potential of this Partnerships for Innovation - Technology Translation (PFI-TT) project is to enhance heart function after a heart attack, using an injectable, regenerative therapeutic. Myocardial ischemia (MI), commonly referred to as a heart attack, is a leading cause of mortality and morbidity in the world. Cell and tissue damage following a heart attack will quickly inhibit the hearts ability to properly pump blood, which in turn can lead to heart failure. While stents and grafts serve to retain heart function, they cannot restore the damage to the heart muscle that has already occurred. The proposed technology helps regenerate heart muscle through injectable treatments to offer partial restoration of lost heart function. This innovation may facilitate viable treatment option for patients contraindicated for stent and/or graft placement, delaying onset of heart failure. The proposed project will develop a strategy to re-vascularize and regenerate cardiac tissues. The proposed technology stimulates stem cells using physiologically-relevant oscillating flow conditions that lead to the secretion of high-quality exosomes or a contained cargo of molecular factors that can regenerate heart muscle. These exosomes will be consolidated in an injectable form for therapeutic delivery to the damaged heart muscle, thereby leading to tissue regeneration and subsequent partial restoration of lost heart function. The proposed work will initiate with rigorous identification of genes and proteins in oscillatory-flow conditioned, stem cell-derived exosomes, demonstrating cargo rich in cardio-regenerative properties. The enhanced exosomes will be injected within an engineered tissue model system platform consisting of differentiated cardiomyocytes within a seeded scaffold mimicking either healthy or ischemic conditions. Cell deformation response from cellular contraction will be longitudinally measured for evidence of improvement in cell contractile function. The effects of oscillatory flow-derived exosome injectable on the cardiomyocytes will be compared to controls that will include: (i) exosomes isolated from static culture, (ii) exosomes secreted by cardiac stem cells, and (iii) healthy/ischemic cardiomyocytes that do not receive any exosomes. 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.

NSF Program Director: Debora Rodrigues