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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Feb 26, 2016; 8(2): 163-179
Published online Feb 26, 2016. doi: 10.4330/wjc.v8.i2.163
Micromanaging cardiac regeneration: Targeted delivery of microRNAs for cardiac repair and regeneration
Jan AAM Kamps, Guido Krenning
Jan AAM Kamps, Endothelial Biomedicine and Vascular Drug Targeting, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands
Guido Krenning, Cardiovascular Regenerative Medicine, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands
Author contributions: Both authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Guido Krenning, PhD, Cardiovascular Regenerative Medicine, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713GZ Groningen, The Netherlands. g.krenning@umcg.nl
Telephone: +31-50-2615181 Fax: +31-50-3619911
Received: July 30, 2015
Peer-review started: July 31, 2015
First decision: September 28, 2015
Revised: October 9, 2015
Accepted: January 5, 2016
Article in press: January 7, 2016
Published online: February 26, 2016
Processing time: 206 Days and 18.4 Hours
Abstract

The loss of cardiomyocytes during injury and disease can result in heart failure and sudden death, while the adult heart has a limited capacity for endogenous regeneration and repair. Current stem cell-based regenerative medicine approaches modestly improve cardiomyocyte survival, but offer neglectable cardiomyogenesis. This has prompted the need for methodological developments that crease de novo cardiomyocytes. Current insights in cardiac development on the processes and regulatory mechanisms in embryonic cardiomyocyte differentiation provide a basis to therapeutically induce these pathways to generate new cardiomyocytes. Here, we discuss the current knowledge on embryonic cardiomyocyte differentiation and the implementation of this knowledge in state-of-the-art protocols to the direct reprogramming of cardiac fibroblasts into de novo cardiomyocytes in vitro and in vivo with an emphasis on microRNA-mediated reprogramming. Additionally, we discuss current advances on state-of-the-art targeted drug delivery systems that can be employed to deliver these microRNAs to the damaged cardiac tissue. Together, the advances in our understanding of cardiac development, recent advances in microRNA-based therapeutics, and innovative drug delivery systems, highlight exciting opportunities for effective therapies for myocardial infarction and heart failure.

Keywords: Cardiac repair; Cellular plasticity; Targeted drug delivery; MicroRNA; Reprogramming

Core tip: Cardiac fibroblast reprogramming into cardiomyocytes holds great promise for future cardiac regenerative medicine therapies. Here, we discuss current advances in the state-of-the-art protocols for the direct reprogramming of cardiac fibroblasts into de novo cardiomyocytes in vitro and in vivo with an emphasis on microRNA-mediated reprogramming. Additionally, we discuss current advances on the state-of-the-art targeted drug delivery systems that can be employed to deliver these microRNAs to the damaged cardiac tissue.