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Cellular Biology of the Heart

Position Papers and Consensus Documents from the ESC Working Group on Cellular Biology of the Heart



Position Paper of the European Society of Cardiology Working Group Cellular Biology of the Heart: cell-based therapies for myocardial repair and regeneration in ischemic heart disease and heart failure

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Authors: Rosalinda Madonna, Linda W. Van Laake, Sean M. Davidson, Felix B. Engel, Derek J. Hausenloy, Sandrine Lecour, Jonathan Leor, Cinzia Perrino, Rainer Schulz, Kirsti Ytrehus, Ulf Landmesser, Christine L. Mummery, Stefan Janssens, James Willerson, Thomas Eschenhagen, Péter Ferdinandy, Joost P.G. Sluijter

Reference: http://dx.doi.org/10.1093/eurheartj/ehw113

First published online: 7 April 2016

Abstract: Despite improvements in modern cardiovascular therapy, the morbidity and mortality of ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and worldwide. Patients with IHD may benefit from therapies that would accelerate natural processes of postnatal collateral vessel formation and/or muscle regeneration. Here, we discuss the use of cells in the context of heart repair, and the most relevant results and current limitations from clinical trials using cell-based therapies to treat IHD and HF. We identify and discuss promising potential new therapeutic strategies that include ex vivo cell-mediated gene therapy, the use of biomaterials and cell-free therapies aimed at increasing the success rates of therapy for IHD and HF. The overall aim of this Position Paper of the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to improve the therapeutic application of cell-based therapies for cardiac regeneration and repair.

Improving the pre-clinical assessment of novel cardioprotective therapies

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Authors: Sandrine Lecour, Hans E. Bøtker, Gianluigi Condorelli, Sean M. Davidson, David Garcia-Dorado, Felix B. Engel, Peter Ferdinandy, Gerd Heusch, Rosalinda Madonna, Michel Ovize, Marisol Ruiz-Meana, Rainer Schulz, Joost P.G. Sluijter, Linda W. Van Laake, Derek M. Yellon, Derek J. Hausenloy

Reference: Cardiovascular Research Journal .doi:10.1093/cvr/cvu225 

First published online: 24 October 2014

Abstract: Ischaemic heart disease (IHD) remains the leading cause of death and disability worldwide. As a result, novel therapies are still needed to protect the heart from the detrimental effects of acute ischaemia–reperfusion injury, in order to improve clinical outcomes in IHD patients. In this regard, although a large number of novel cardioprotective therapies discovered in the research laboratory have been investigated in the clinical setting, only a few of these have been demonstrated to improve clinical outcomes. One potential reason for this lack of success may have been the failure to thoroughly assess the cardioprotective efficacy of these novel therapies in suitably designed preclinical experimental animal models. Therefore, the aim of this Position Paper by the European Society of Cardiology Working Group Cellular Biology of the Heart is to provide recommendations for improving the preclinical assessment of novel cardioprotective therapies discovered in the research laboratory, with the aim of increasing the likelihood of success in translating these new treatments into improved clinical outcomes.

Translating cardioprotection for patient benefit

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Authors : Hausenloy DJ, Erik Bøtker H, Condorelli G, Ferdinandy P, Garcia-Dorado D, Heusch G, Lecour S, van Laake LW, Madonna R, Ruiz-Meana M, Schulz R, Sluijter JP, Yellon DM, Ovize M.

Reference: Cardiovasc Research Journal. 2013 Apr 1; 98(1):7-27. doi: 10.1093/cvr/cvt004. Epub 2013

First time published: 19 January 2013

Summary: Coronary heart disease (CHD) is the leading cause of death and disability worldwide. Despite current therapy, the morbidity and mortality for patients with CHD remains significant. The most important manifestations of CHD arise from acute myocardial ischaemia–reperfusion injury (IRI) in terms of cardiomyocyte death and its long-term consequences. As such, new therapeutic interventions are required to protect the heart against the detrimental effects of acute IRI and improve clinical outcomes. Although a large number of cardioprotective therapies discovered in preclinical studies have been investigated in CHD patients, few have been translated into the clinical setting, and a significant number of these have failed to show any benefit in terms of reduced myocardial infarction and improved clinical outcomes. Because of this, there is currently no effective therapy for protecting the heart against the detrimental effects of acute IRI in patients with CHD. One major factor for this lack of success in translating cardioprotective therapies into the clinical setting can be attributed to problems with the clinical study design. Many of these clinical studies have not taken into consideration the important data provided from previously published pre-clinical and clinical studies. The overall aim of this ESC Working Group Cellular Biology of the Heart Position Paper is to provide recommendations for optimizing the design of clinical cardioprotection studies, which should hopefully result in new and effective therapeutic interventions for the future benefit of CHD patients.

Post-conditioning and protection from reperfusion inury: where do we stand?

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Authors: Michel Ovize, Gary F. Baxter, Fabio Di Lisa, Peter Ferdinandy,
David Garcia-Dorado, Derek J. Hausenloy, Gerd Heusch, Jakob Vinten-Johansen,
Derek M. Yellon, and Rainer Schulz

Reference: Cardiovasc Research Journal (2010) 87 (3): 406-423. doi: 10.1093/cvr/cvq129

First time published: 6 May 2010

Abstract: Ischaemic postconditioning (brief periods of ischaemia alternating with brief periods of reflow applied at the onset of reperfusion following sustained ischaemia) effectively reduces myocardial infarct size in all species tested so far, including humans. Ischaemic postconditioning is a simple and safe manoeuvre, but because reperfusion injury is initiated within minutes of reflow, postconditioning must be applied at the onset of reperfusion. The mechanisms of protection by postconditioning include: formation and release of several autacoids and cytokines; maintained acidosis during early reperfusion; activation of protein kinases; preservation of mitochondrial function, most strikingly the attenuation of opening of the mitochondrial permeability transition pore (MPTP). Exogenous recruitment of some of the identified signalling steps can induce cardioprotection when applied at the time of reperfusion in animal experiments, but more recently cardioprotection was also observed in a proof-of-concept clinical trial. Indeed, studies in patients with an acute myocardial infarction showed a reduction of infarct size and improved left ventricular function when they underwent ischaemic postconditioning or pharmacological inhibition of MPTP opening during interventional reperfusion. Further animal studies and large-scale human studies are needed to determine whether patients with different co-morbidities and co-medications respond equally to protection by postconditioning. Also, our understanding of the underlying mechanisms must be  improved to develop new therapeutic strategies to be applied at reperfusion with the ultimate aim of limiting the burden of ischaemic heart disease and potentially providing protection for other organs at risk of reperfusion injury, such as brain and kidney.