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Direct cellular reprogramming for cardiac repair and regeneration

Lookup NU author(s): Dr Jonathan Batty, Professor Vijay KunadianORCiD

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Abstract

Heart failure is a major cause of morbidity and mortality, characterized by depletion of functioning cardiomyocytes, myocardial remodelling, and impaired contractile function. As the heart has a limited capacity for repair, and current treatments do not reverse myocardial attrition, novel regenerative strategies are imperative. Although cell delivery-based approaches remain promising, in situ reprogramming of endogenous cardiac fibroblasts (which are pathophysiologically implicated in cardiac remodelling) into functional cardiomyocytes may represent an advantageous approach. Several groups report successful in vitro and in vivo reprogramming of murine fibroblasts, using critical transcription factors, microRNA mimics, and small molecules, to cells demonstrating cardiomyocyte-like morphology, gene expression, and spontaneous contraction, which improve cardiac function in post-infarct models. Although proof-of-concept studies demonstrate reprogramming in human fibroblasts, significant barriers to therapeutic reprogramming remain. In this review, we evaluate the current status of reprogramming strategies for cardiac repair, and explore future perspectives within the context of clinical translation.

Publication metadata

Author(s): Batty JA, Lima JAC, Kunadian V

Publication type: Review

Publication status: Published

Journal: European Journal of Heart Failure

Year: 2016

Volume: 18

Issue: 2

Pages: 145-156

Print publication date: 01/02/2016

Online publication date: 03/12/2015

Acceptance date: 22/10/2015

ISSN (print): 1388-9842

ISSN (electronic): 1879-0844

Publisher: WILEY-BLACKWELL

URL: http://dx.doi.org/10.1002/ejhf.446

DOI: 10.1002/ejhf.446

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