title: Direct cellular reprogramming for cardiac repair and regeneration.
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.
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.|Royal Victoria Infirmary, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Batty
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Jose A C
authors.initials: JA
authors.lastname: Lima
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.|Freeman Hospital, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kunadian
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D017690:Cell Transplantation; D065150:Cellular Reprogramming / Q000235:genetics; D005260:Female; D006321:Heart / Q000502:physiology*; D006333:Heart Failure / Q000628:therapy*; D006801:Humans; D008297:Male; D032383:Myocytes, Cardiac / Q000502:physiology / Q000637:transplantation*; D012038:Regeneration / Q000235:genetics
keywords: Cellular reprogramming; Heart failure; Molecular and cellular biology; Pathophysiology; Regenerative medicine