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R. Contexte, Plusieurs études réalisées chez le rongeur suggèrent que 1) les cardiosphères pourraient avoir un potentiel thérapeutique supérieur à celui des CDCs, 2) les exosomes sécrétés par les CDCs seraient les médiateurs des effets observés et 3) l'injection des exosomes seuls pourrait mimer les effets des CDCs. L'objectif de cette thèse a donc été d'évaluer les effets des cardiosphères et des exosomes sécrétés, Parmi les nouveaux traitements de l'infarctus du myocarde, les cellules d'origine cardiaque dérivées des cardiosphères (CDCs) semblent prometteuses

, Méthodes : La taille des cardiosphères a été optimisée en modifiant les conditions de culture. Les cardiosphères obtenues ont ensuite été administrées par voie intra-coronaire chez des porcs sains puis chez des animaux ayant subi un

, La dose ainsi que les modalités d'administration (intra-coronaire ou intra-myocardique) ont été déterminées dans un modèle d'ischémie reperfusion puis une étude randomisée contre placebo a été réalisée dans un modèle d'infarctus constitué. Le critère de jugement choisi a été la diminution de taille de la lésion d'infarctus mesurée par l'IRM pour les modèles d, Dans une deuxième étude, des exosomes sécrétés par les CDCs ont été testés

, Ces cardiosphères permettaient de bloquer le processus de remodelage inverse (préservation de la fraction d'éjection et de la fonction segmentaire) et de diminuer la taille de la zone infarcie. De plus, la perfusion coronaire mesurée de manière invasive et par IRM était améliorée. L'analyse histologique a confirmé ces données en montrant une diminution de la fibrose et une augmentation de la densité vasculaire. En revanche, l'administration par voie intra-coronaire des exosomes ne permettait pas de diminuer la taille d'infarctus alors que leur administration intra-myocardique le permettait (dans l'ischémie reperfusion et l'infarctus constitué). Cette diminution de taille d'infarctus s'accompagnait d'une préservation de la fraction d'éjection. Sur le plan histologique, ces modifications de fonction s'accompagnaient d'une diminution de l'inflammation, Résultats : L'optimisation des conditions de culture des cardiosphères a permis une perfusion par voie intra-coronaire sans risque chez les animaux sains et infarcis

, De plus l'optimisation de leur taille permet une délivrance sans risque par voie intracoronaire. Les exosomes peuvent remplacer les cellules dans l'ischémie reperfusion et dans l, Conclusion : Les cardiosphères permettent une diminution de la taille de l'infarctus et du remodelage inverse

, Mots clés : thérapie cellulaire ; Infarctus du myocarde ; modèles animaux ; exosomes