Cardiac regenerative medicine: At the crossroad of microRNA function and biotechnology

Abstract

There is an urgent need to develop new therapeutic strategies to stimulate cardiac repair after damage, such as myocardial infarction. Already for more than a century scientist are intrigued by studying the regenerative capacity of the heart. While moving away from the old classification of the heart as a post-mitotic organ, and being inspired by the stem cell research in other scientific fields, mainly three different strategies arose in order to develop regenerative medicine, namely; the use of cardiac stem cells, reprogramming of fibroblasts into cardiomyocytes or direct stimulation of endogenous cardiomyocyte proliferation. MicroRNAs, known to play a role in orchestrating cell fate processes such as proliferation, differentiation and reprogramming, gained a lot of attention in this context the latest years. Indeed, several research groups have independently demonstrated that microRNA-based therapy shows promising results to induce heart tissue regeneration and improve cardiac pump function after myocardial injury. Nowadays, a whole new biotechnology field has been unveiled to investigate the possibilities for efficient, safe and specific delivery of microRNAs towards the heart.

Therapeutic Delivery of miR-148a Suppresses Ventricular Dilation in Heart Failure

“…AAV vectors are increasingly recognized as reliable tool for research purposes due to their low immunogenicity, tissue tropism, and relative safety due to their low rate of genomic integration. 29 , 30 Specifically, AAV vectors of serotype 1/6/9 (AAV1/6/9) that display varying ranges of cardiac tropism, are used to deliver a variety of therapeutic genes, including small functional non-coding RNAs such as microRNAs. Future improvement of AAV vectors should address their limited capacity to carry transgenes of larger sizes.…”

Platelet-Rich Plasma for Heart Cell Regeneration Post-myocardial Infarction: A Propitious Therapeutic Approach

“…Another method is cell-based therapies, such as transplantation of human pluripotent stem cell-derived cardiomyocytes, that have demonstrated potential in treating myocardial abnormalities [17]. Following myocardial damage, microRNA-based therapy has demonstrated encouraging outcomes in promoting heart tissue regeneration and enhancing cardiac pump function [18].…”

Combining Nanomaterials and Developmental Pathways to Design New Treatments for Cardiac Regeneration: The Pulsing Heart of Advanced Therapies

“…Because of their regulatory role in cell fate, miRNAs are considered interesting molecular tools and new potent drugs for a number of diseases (Raso and Dirkx, 2017). miRNAs are small endogenous non-coding RNAs (∼23 nucleotides) that play gene-regulatory roles in plants and animals by directing the post-transcriptional repression of proteincoding mRNAs (Bartel, 2009).…”