USE OF A DECELLULARISED HUMAN EXTRACELLULAR MATRIX AS A BIOLOGICAL SCAFFOLD TO SUPPORT EPICARDIUM-MEDIATED CARDIAC REGENERATION

The project aims to explore the use of a decellularized human extracellular matrix (ECM) as a support to promote epicardial-mediated cardiac regeneration. Heart failure, often resulting from acute myocardial infarction, represents a significant clinical challenge. Despite advances in therapies, the replacement of damaged cardiac tissue with non-functional fibrotic tissue inevitably leads to heart failure.

Cardiac progenitor cells (CPCs) present in adult heart tissue offer potential for regeneration. However, the lack of regenerative capacity of myocardial cells is a major challenge. The project focuses on the communication between CPCs and the extracellular matrix, recognizing the crucial role it plays in modulating the biological phenotype of CPCs.

Previous studies have identified c-kit-positive cardiovascular precursors in the adult epicardium, involved in regeneration after infarction. The activation of these cells during the infarction, with their proliferation and differentiation, offers an interesting perspective for cardiac regeneration.

The study intends to explore how different decellularized human extracellular matrices (dermis, healthy heart, decompensated heart) can influence the activation of epicardial cells through the process of epithelial-mesenchymal transition (EMT). We also aim to identify the matrix-specific factors responsible for this activation.

Through the use of the secretome of epicardial cells conditioned with different matrices, the project aims to demonstrate the cytoprotective paracrine influence on cardiomyocytes and support for regeneration. Analysis of FSTL-1 levels in the secretome will confirm its involvement in epicardial EMT and regeneration.

Participants:

• Dr. Eleonora Foglio, PhD (Technoscience, Pontino Science and Technology Park, Latina, Italy)
• Prof. ssa Federica Limana, PhD (San Raffaele University of Rome, Rome, Italy; Laboratory of Cellular and Molecular Pathology, IRCCS San Raffaele Roma, Italy)
• Prof. Marco Tafani, PhD (Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy)
• Prof. Matteo Antonio Russo, MD (IRCCS San Raffaele Roma and MEBIC Consortium, Rome, Italy; San Raffaele University of Rome, Rome, Italy)

The project aims to provide new perspectives in cardiac regeneration, exploring the key role of the extracellular matrix as a support to activate the regenerative potential of cardiac progenitor cells.