The Evolution of the Stem Cell Theory for Heart Failure

ABSTRACTVarious stem cell-based approaches for cardiac repair have achieved encouraging results in animal experiments, often leading to their rapid proceeding to clinical testing. However, freewheeling evolutionary developments of the stem cell theory might lead to dystopian scenarios where heterogeneous sources of therapeutic cells could promote mixed clinical outcomes in un-stratified patient populations. This review focuses on the lessons that should be learnt from the first generation of stem cell-based strategies and emphasizes the absolute requirement to better understand the basic mechanisms of stem cell biology and cardiogenesis. We will also discuss about the unexpected “big bang” in the stem cell theory, “blasting” the therapeutic cells to their unchallenged ability to release paracrine factors such as extracellular membrane vesicles. Paradoxically, the natural evolution of the stem cell theory for cardiac regeneration may end with the development of cell-free strategies with multiple cellular targets including cardiomyocytes but also other infiltrating or resident cardiac cells

Guidelines for translational research in heart failure

Heart failure (HF) remains a major cause of death and hospitalization worldwide. Despite medical advances, the prognosis of HF remains poor and new therapeutic approaches are urgently needed. The development of new therapies for HF is hindered by inappropriate or incomplete preclinical studies. In these guidelines, we present a number of recommendations to enhance similarity between HF animal models and the human condition in order to reduce the chances of failure in subsequent clinical trials. We propose different approaches to address safety as well as efficacy of new therapeutic products. We also propose that good practice rules are followed from the outset so that the chances of eventual approval by regulatory agencies increase. We hope that these guidelines will help improve the translation of results from animal models to humans and thereby contribute to more successful clinical trials and development of new therapies for HF.European Union [CardioNeT-ITN-289600, CardioNext-ITN-608027, FP7-IMI-JU-SAFET-115003]; Spanish Ministry of Economy [SAF2012-31451]; Regional Government of Madrid [2010-BMD-2321]; Spanish Ministry of Economy; Pro-CNIC Foundation; NIH [HL-120732, HL100401]; AHA [14SFRN20740000]; CPRIT [RP110486P3]; Leducq Foundation [11CVD04]; MINECO-SAF [2013-42962R]; Instituto Carlos III [TERCEL-RD-12/00190026, RIC12/00420024]S

Predictors of contemporary coronary artery bypass grafting outcomes

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Fibers for hearts: A critical review on electrospinning for cardiac tissue engineering

Cardiac cell therapy holds a real promise for improving heart function and especially of the chronically failing myocardium. Embedding cells into 3D biodegradable scaffolds may better preserve cell survival and enhance cell engraftment after transplantation, consequently improving cardiac cell therapy compared with direct intramyocardial injection of isolated cells. The primary objective of a scaffold used in tissue engineering is the recreation of the natural 3D environment most suitable for an adequate tissue growth. An important aspect of this commitment is to mimic the fibrillar structure of the extracellular matrix, which provides essential guidance for cell organization, survival, and function. Recent advances in nanotechnology have significantly improved our capacities to mimic the extracellular matrix. Among them, electrospinning is well known for being easy to process and cost effective. Consequently, it is becoming increasingly popular for biomedical applications and it is most definitely the cutting edge technique to make scaffolds that mimic the extracellular matrix for industrial applications. Here, the desirable physico-chemical properties of the electrospun scaffolds for cardiac therapy are described, and polymers are categorized to natural and synthetic.Moreover, the methods used for improving functionalities by providing cells with the necessary chemical cues and a more in vivo- like environment are reported

Les cellules souches embryonnaires dans le traitement de l’insuffisance cardiaque sévère

L’expérience acquise en thérapie cellulaire cardiaque suggère que la régénération de zones étendues de myocarde nécrosé ne peut sans doute pas procéder des seuls effets paracrines des cellules greffées mais requiert la transformation de ces cellules en cardiomyocytes capables de remplacer fonctionnellement ceux qui ont été perdus. C’est dans cette perspective que se justifie l’utilisation de cellules souches embryonnaires humaines dont la pluripotence permet une telle différenciation. Les résultats expérimentaux obtenus sur des modèles animaux d’infarctus du myocarde sont encourageants mais le passage à l’Homme exige que soient encore résolus plusieurs problèmes dont les plus importants sont l’optimisation de la spécification cardiaque des cellules, la sélection des progéniteurs ainsi obtenus afin de ne greffer qu’une population purifiée et non contaminée par des cellules pluripotentes résiduelles auxquelles est attaché un risque tumoral et, enfin, la maîtrise du rejet attendu de ces cellules allogéniques par des méthodes cliniquement acceptables. Si la solution de ces problèmes est un pré-requis absolu, le succès thérapeutique de cette approche dépend aussi de la capacité à développer des stratégies permettant un transfert efficient des cellules dans le tissu cible, le maintien de leur survie et leur organisation spatiale compatible avec une contribution à la fonction contractile du cœur

Les cellules souches pluripotentes dans le traitement de l’insuffisance cardiaque: Statut actuel, problèmes et perspectives

International audienceBien que les premiers essais de thérapie cellulaire dans l’insuffisance cardiaque se soient soldés pour la plupart par une absence d’améliorations cliniquement pertinentes, des signaux encourageants ont commencé à émerger, signaux qui suggèrent que les cellules souches, ou leurs produits de sécrétion, pourraient finalement trouver leur place dans l’arsenal des traitements proposables aux patients atteints d’insuffisance cardiaque. Dans ce cadre, les cellules souches pluripotentes suscitent un intérêt particulier en raison de leur capacité unique à donner naissance à des cellules spécifiques d’un lignage donné et transplantables au stade de différenciation souhaité. Cette revue discute l’état actuel de la recherche dans ce domaine, les problèmes qui restent à résoudre et les approches susceptibles d’accélérer les applications cliniques de ce type cellulaire