INFORMAZIONI SU
CARPI Giada
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Supervisore: Prof. Beltrami EXTREMEHEART-EXTRacellular vEsicle-mediated transplantation of Mitochondria to rEscue end-stage failing HEARTs |
| Heart failure (HF) has an estimated prevalence of 3-20 cases/1000 population with a progression to an advanced stage complicated by high mortality in 1-10% of cases. Pharmacological and mechanical aids have been shown to improve survival and quality of life, but about 20% of patients on the heart transplant waiting list die while waiting for a compatible organ or become too sick to be a good candidate. Mitochondria play a crucial role in the irreversibile loss of cardiac tissue after ischemia/riperfusion injury. EXTREMEHEART will study the safety and the efficacy of personalized mitochondria-rich extracellular vescicles cardiac transplantation in a clinically relevant animal model of advanced HF and in a human end-stage failing heart. The results will be helpful to improve survival and quality of life of patients in waiting list for heart transplantation who do not adequately respond to inotropes or mechanical circulatory support. The project is divided into 3 workpackages, which objectives are: 1. tecnically optimize the delivery of naked mitochondria and mitochondria-rich extracellular vesicles into target cells, as well as the collection and the preservation of mitochondria for delayed delivery; obtainig also insights into the mechanism of action of mitochondrial transplantation in cellular models of cardiac injury. 2. assess the potential of the cardiac transplantation of mitochondria-rich extracellular vesicles to reverse remodeling in a model of heart failure in male and female old rats, evaluating also the best route of administration. 3. provide the first proof of principle that mitochondria can be transferred into the cells of a pathological human heart after ischemia/reperfusion injury, employing an ex vivo perfusion model. | |