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

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

doi:10.1093/eurheartj/ehw113

Cited by 223 publications

(254 citation statements)

References 188 publications

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“…This finding clearly demands the implementation of personalized cardiac SC therapies in which the selection of SC source, modification and application is subjected to these individual characteristics [525]. Thus, prospective research should focus on the development of specific responder scores and the identification of prognostic biomarkers to identify patient cohorts who benefit most from distinct SC treatments [526,527]. Thereby, a higher standardization of study designs and the establishment of a global open-access database for the registration and publication of preclinical and clinical trials would greatly improve the comparability and access of obtained data [526,528,529].…”

Section: Resultsmentioning

confidence: 99%

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

Müller

Lemcke

Dávid

2018

Cell Physiol Biochem

174

140

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A large number of clinical trials have shown stem cell therapy to be a promising therapeutic approach for the treatment of cardiovascular diseases. Since the first transplantation into human patients, several stem cell types have been applied in this field, including bone marrow derived stem cells, cardiac progenitors as well as embryonic stem cells and their derivatives. However, results obtained from clinical studies are inconsistent and stem cell-based improvement of heart performance and cardiac remodeling was found to be quite limited. In order to optimize stem cell efficiency, it is crucial to elucidate the underlying mechanisms mediating the beneficial effects of stem cell transplantation. Based on these mechanisms, researchers have developed different improvement strategies to boost the potency of stem cell repair and to generate the “next generation” of stem cell therapeutics. Moreover, since cardiovascular diseases are complex disorders including several disease patterns and pathologic mechanisms it may be difficult to provide a uniform therapeutic intervention for all subgroups of patients. Therefore, future strategies should aim at more personalized SC therapies in which individual disease parameters influence the selection of optimal cell type, dosage and delivery approach.

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Section: Resultsmentioning

confidence: 99%

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

Müller

Lemcke

Dávid

2018

Cell Physiol Biochem

174

140

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“…However, the benefits of SCs have been attributed to their paracrine effects, which could be mediated by exosomes[64,72]. Following the observation that the SCs remain at the site of injection release factors mediating this paracrine effect, exosomes have been proposed as important potential paracrine mediators for myocardial regeneration.…”

Section: Exosomes As Emerging Tools For Post-myocardial Infarction Rementioning

confidence: 99%

Stem cell-derived exosomes - an emerging tool for myocardial regeneration

Lázár

Benedek

Korodi

et al. 2018

WJSC

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Cardiovascular diseases (CVDs) continue to represent the number one cause of death and disability in industrialized countries. The most severe form of CVD is acute myocardial infarction (AMI), a devastating disease associated with high mortality and disability. In a substantial proportion of patients who survive AMI, loss of functional cardiomyocytes as a result of ischaemic injury leads to ventricular failure, resulting in significant alteration to quality of life and increased mortality. Therefore, many attempts have been made in recent years to identify new tools for the regeneration of functional cardiomyocytes. Regenerative therapy currently represents the ultimate goal for restoring the function of damaged myocardium by stimulating the regeneration of the infarcted tissue or by providing cells that can generate new myocardial tissue to replace the damaged tissue. Stem cells (SCs) have been proposed as a viable therapy option in these cases. However, despite the great enthusiasm at the beginning of the SC era, justified by promising initial results, this therapy has failed to demonstrate a significant benefit in large clinical trials. One interesting finding of SC studies is that exosomes released by mesenchymal SCs (MSCs) are able to enhance the viability of cardiomyocytes after ischaemia/reperfusion injury, suggesting that the beneficial effects of MSCs in the recovery of functional myocardium could be related to their capacity to secrete exosomes. Ten years ago, it was discovered that exosomes have the unique property of transferring miRNA between cells, acting as miRNA nanocarriers. Therefore, exosome-based therapy has recently been proposed as an emerging tool for cardiac regeneration as an alternative to SC therapy in the post-infarction period. This review aims to discuss the emerging role of exosomes in developing innovative therapies for cardiac regeneration as well as their potential role as candidate biomarkers or for developing new diagnostic tools.

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“…These beneficial effects are probably due to the indirect paracrine capacity of transplanted stem cells to facilitate endogenous cardiac repair processes, having demonstrated safety and modest efficacy in phase III clinical trials. At present, technical challenges still limit stem cell use in human studies [164,165], with these challenges including poor definition of the cell types used, the diversity in cell-handling procedures, and functional variability intrinsic to autologous-derived cells thus limiting factors of cell-based therapies [160]. …”

Section: Strategies To Improve Cell Regeneration and Repairmentioning

confidence: 99%

New Treatment Strategies for Alcohol-Induced Heart Damage

Fernández‐Solà

Porta

2016

IJMS

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High-dose alcohol misuse induces multiple noxious cardiac effects, including myocyte hypertrophy and necrosis, interstitial fibrosis, decreased ventricular contraction and ventricle enlargement. These effects produce diastolic and systolic ventricular dysfunction leading to congestive heart failure, arrhythmias and an increased death rate. There are multiple, dose-dependent, synchronic and synergistic mechanisms of alcohol-induced cardiac damage. Ethanol alters membrane permeability and composition, interferes with receptors and intracellular transients, induces oxidative, metabolic and energy damage, decreases protein synthesis, excitation-contraction coupling and increases cell apoptosis. In addition, ethanol decreases myocyte protective and repair mechanisms and their regeneration. Although there are diverse different strategies to directly target alcohol-induced heart damage, they are partially effective, and can only be used as support medication in a multidisciplinary approach. Alcohol abstinence is the preferred goal, but control drinking is useful in alcohol-addicted subjects not able to abstain. Correction of nutrition, ionic and vitamin deficiencies and control of alcohol-related systemic organ damage are compulsory. Recently, several growth factors (myostatin, IGF-1, leptin, ghrelin, miRNA, and ROCK inhibitors) and new cardiomyokines such as FGF21 have been described to regulate cardiac plasticity and decrease cardiac damage, improving cardiac repair mechanisms, and they are promising agents in this field. New potential therapeutic targets aim to control oxidative damage, myocyte hypertrophy, interstitial fibrosis and persistent apoptosis In addition, stem-cell therapy may improve myocyte regeneration. However, these strategies are not yet approved for clinical use.

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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

Cited by 223 publications

References 188 publications

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

Stem cell-derived exosomes - an emerging tool for myocardial regeneration

New Treatment Strategies for Alcohol-Induced Heart Damage

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