Cardiac Regeneration After Myocardial Infarction: an Approachable Goal
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MYOCARDIAL DISEASE (A ABBATE AND G SINAGRA, SECTION EDITORS)
Cardiac Regeneration After Myocardial Infarction: an Approachable Goal Mauro Giacca 1,2
# The Author(s) 2020
Abstract Purpose of Review Until recently, cardiac regeneration after myocardial infarction has remained a holy grail in cardiology. Failure of clinical trials using adult stem cells and scepticism about the actual existence of such cells has reinforced the notion that the heart is an irreversibly post-mitotic organ. Recent evidence has drastically challenged this conclusion. Recent Findings Cardiac regeneration can successfully be obtained by at least two strategies. First, new cardiomyocytes can be generated from embryonic stem cells or induced pluripotent stem cells and administered to the heart either as cell suspensions or upon ex vivo generation of contractile myocardial tissue. Alternatively, the endogenous capacity of cardiomyocytes to proliferate can be stimulated by the delivery of individual genes or, more successfully, of selected microRNAs. Summary Recent experimental success in large animals by both strategies now fuels the notion that cardiac regeneration is indeed possible. Several technical hurdles, however, still need to be addressed and solved before broad and successful clinical application is achieved. Keywords Cardiomyocyte . Myocardial infarction . microRNA . Lipid nanoparticle . Regeneration . Stem cells
Introduction The need to develop novel therapies for heart failure (HF) consequent to myocardial infarction (MI) is impelling. Despite notable progress in the application of devices assisting the failing myocardium [1], HF prognosis remains poor, with mortality estimated at 40% of patients at only 4 years from diagnosis [2]. This is worse than several common cancers. HF is also tremendously expensive, representing 2–3% of national health expenditures in high-income countries, projected to more than doubling in the next 20 years [3, 4]. Most notably, pharmacological treatment of HF uses drugs that have only marginally evolved since the mid-1990s. While
high hope is now raised by the unpredicted and somehow surprising cardiovascular effects of SGLT2 inhibitors [5], for which no convincing molecular explanation yet exists, no conceptually novel drugs have been introduced in the management of patients with HF since the angiotensin II receptor blockers [6]. The relatively novel angiotensin receptorneprilysin inhibitor (ARNI) combination [7] is based on drugs that were both individually developed in the 1990s. In addition, a number of drugs have so far failed in Phase III clinical trials [8]. Even more remarkably, for conditions that are as prevalent as MI and HF, no biological therapy has yet been developed, based on any protein, peptide, antibody, or nucleic acid [9].
The Problems of Cardiomyocyte Loss This article is part of the Topical Collection on Myocardial Disease * Mauro Giacca [email protected] 1
King’s College London, British Heart Foundation Centre of Research Excellence, School of Cardiovascular Medicine &
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