Abstract

EXTREMEHEART is capable of tackling the complexities of management of end-stage heart failure (HF) and cardiac recovery of patients waiting for heart transplantation (HTx) at a level and dimension currently not existing in hospital setting. It aims to optimize, validate and exploit personalized approach of mitochondria-rich extracellular vesicles (EV) cardiac transplantation as bridge-to-transplant in the clinic, based on precise experimental findings, development of therapeutic and monitoring procedures, rigorous pre-clinical evaluation and appropriate consideration of diversity aspects. The EXTREMEHEART consortium brings together internationally recognized experts from Italian academic and clinical sectors and assimilates knowledge from diverse disciplines to provide high level interdisciplinary and intersectoral research environment, in a field of high priority for society, academia and industry. Heart failure (HF), indeed, has an estimated prevalence of 3-20 cases/1,000 population with a progression to an advanced stage, complicated by high mortality, in 1-10% of cases. Although pharmacological and mechanical aids have been shown to improve survival and quality of life, 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 for the complex transplant procedure due to donor shortages. Since mitochondria play a crucial role in the irreversible loss of cardiac tissue after ischemia/reperfusion (IR) injury, the extent of mitochondrial damage is a key determinant in the progression of heart failure to Stage D. Therefore, the development of personalized transfer of healthy mitochondria into resident cells of advanced failing heart may increase resilience against deterioration during the waiting time thus optimizing the donor/recipient matching. EXTREMEHEART will study, for the first time, the safety and efficacy of personalized mitochondria-rich EV cardiac transplantation in a clinically relevant animal model of advanced HF and in human end-stage failing heart even by employing ex vivo perfusion system. We pointed to combine different methods to optimize mitochondrial transplantation including isolation of these organelles from allogeneic cells, cryopreservation in liquid nitrogen and extravesicular-mediated transfer of mitochondria to preserve their function over time. The precision procedures used to store and transport mitochondria from the site of their isolation to remotely localized operating rooms, maintaining their function for a long time, remains a desirable goal since it will increase the quality and efficacy of cardiac mitochondria transplantation in a hospital setting. Our results will be helpful to open new avenues in the treatment of patients candidate to HTx.

Partenariato

• Università degli Studi di Udine
• Scuola Superiore di Studi Universitari e Perfezionamento Sant’Anna di Pisa

Importo del progetto

Importo totale del progetto        Euro 126.992,80
Importo del progetto Uniud        Euro 109.344,80
Finanziamento Uniud                Euro 17.578,00

Durata

• Dal 16/10/2023
• Al 15/10/2025

Link

https://prin.mur.gov.it/