Direct Cardiac Reprogramming with Engineered miRNA Scaffolds

Abstract

Ischemic heart disease is a predominant cause of death worldwide. The loss or death of cardiomyocytes due to restricted blood flow often results in a cardiac injury. Myofibroblasts replace these injured cardiomyocytes to preserve structural integrity. However, the depleted cardiomyocytes lead to cardiac dysfunction such as pathological cardiac dilation, reduced cardiac contraction, and fibrosis. Repair and regeneration of myocardium are the best possible therapy for end-stage heart failure patients because the current cardiomyocytes restoration therapies are limited to heart transplantation only. The emergence of interests to directly reprogram a mammalian heart with minimal regenerative capacity holds a promising future in the field of cardiovascular regenerative medicine. Repair and regeneration become the two crucial factors in the field of cardiovascular regenerative medicine since heart muscles have no substitutes, like heart valves or blood vessels. Cardiac regeneration includes strategies to reprogram with diverse factors like small molecules, genetic and epigenetic regulators. However, there are some constraints like low efficacy, immunogenic problems, and unsafe delivery systems that pose a daunting challenge in human trial translations. Hence, there is a need for a holistic nanoscale approach in regulating cell fate effectively and efficiently with a safer delivery and a suitable microenvironment that mimics the extracellular matrix. In this review, we have discussed the current state-of-the-art techniques, challenges in direct reprogramming of fibroblasts to cardiac muscle, and prospects of biomaterials in miRNA delivery and cardiac regeneration predominantly during the past decade (2008-2019).

Keywords: Direct reprogramming; cardiac tissue engineering; miRNA; miRNA delivery; myofibroblasts; scaffolds.