Study of the direct reprogramming of cardiac fibroblasts in cardiomyocytes via polymeric nanoparticles releasing microRNA.

Myocardial infarction represents one of the main causes of death in the world. It is caused by coronary occlusion to blood flow, and leads to irreversible cardiomyocytes death. Myocardium does not regenerate, while a fibrotic scar forms: it is stiffer than normal tissue, mainly composed by myofibroblasts and, in most cases, its formation leads to heart failure. Nowadays, cardiac regenerative therapies do not exist, while mortality rate after myocardial infarction is still high. Therefore, new regenerative approaches are under study. One novel interesting research approach is based on cell reprogramming aimed at modifying the cell phenotype from fibroblasts into cardiomyocytes. This thesis work was aimed at the design of new nanomedicine approaches for miRNA delivery for the direct reprogramming of cardiac fibroblasts into cardiomyocytes. The nanoparticles were initially prepared and physico-chemically characterized compared to a commercial transfectant agent, by measuring their size, PDI, Z-potential, encapsulation efficiency and miRNAs release. Then, in vitro experiments on cardiac fibroblasts were performed to study the biological response of cells to transfection with miRNA-loaded nanoparticle. The work has been carried out within the BIORECAR ERC project (grant agreement 772168).