103 research outputs found
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 âbig bangâ in the stem cell theory, âblastingâ 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
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 lâinsuffisance cardiaque sĂ©vĂšre
LâexpĂ©rience acquise en thĂ©rapie cellulaire cardiaque suggĂšre que la rĂ©gĂ©nĂ©ration de zones Ă©tendues de myocarde nĂ©crosĂ© ne peut sans doute pas procĂ©der des seuls effets paracrines des cellules greffĂ©es mais requiert la transformation de ces cellules en cardiomyocytes capables de remplacer fonctionnellement ceux qui ont Ă©tĂ© perdus. Câest dans cette perspective que se justifie lâutilisation de cellules souches embryonnaires humaines dont la pluripotence permet une telle diffĂ©renciation. Les rĂ©sultats expĂ©rimentaux obtenus sur des modĂšles animaux dâinfarctus du myocarde sont encourageants mais le passage Ă lâHomme exige que soient encore rĂ©solus plusieurs problĂšmes dont les plus importants sont lâoptimisation de la spĂ©cification cardiaque des cellules, la sĂ©lection des progĂ©niteurs ainsi obtenus afin de ne greffer quâune population purifiĂ©e et non contaminĂ©e par des cellules pluripotentes rĂ©siduelles auxquelles est attachĂ© un risque tumoral et, enfin, la maĂźtrise du rejet attendu de ces cellules allogĂ©niques par des mĂ©thodes cliniquement acceptables. Si la solution de ces problĂšmes est un prĂ©-requis absolu, le succĂšs thĂ©rapeutique de cette approche dĂ©pend aussi de la capacitĂ© Ă dĂ©velopper des stratĂ©gies permettant un transfert efficient des cellules dans le tissu cible, le maintien de leur survie et leur organisation spatiale compatible avec une contribution Ă la fonction contractile du cĆur
Les cellules souches pluripotentes dans le traitement de lâinsuffisance cardiaque: Statut actuel, problĂšmes et perspectives
International audienceBien que les premiers essais de thĂ©rapie cellulaire dans lâinsuffisance cardiaque se soient soldĂ©s pour la plupart par une absence dâamĂ©liorations cliniquement pertinentes, des signaux encourageants ont commencĂ© Ă Ă©merger, signaux qui suggĂšrent que les cellules souches, ou leurs produits de sĂ©crĂ©tion, pourraient finalement trouver leur place dans lâarsenal des traitements proposables aux patients atteints dâinsuffisance cardiaque. Dans ce cadre, les cellules souches pluripotentes suscitent un intĂ©rĂȘt particulier en raison de leur capacitĂ© unique Ă donner naissance Ă des cellules spĂ©cifiques dâun lignage donnĂ© et transplantables au stade de diffĂ©renciation souhaitĂ©. Cette revue discute lâĂ©tat actuel de la recherche dans ce domaine, les problĂšmes qui restent Ă rĂ©soudre et les approches susceptibles dâaccĂ©lĂ©rer les applications cliniques de ce type cellulaire
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