Mesenchymal stem cells-derived exosomes as paracrine effectors for cardioprotection after Acute Myocardial Infarction

• Grant number: 17/17296-0
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): March 01, 2018
• Effective date (End): August 31, 2019
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: José Eduardo Krieger
• Grantee: Nathalia Corrêa de Almeida Oliveira
• Home Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/17368-0 - Cardiovascular genomics: mechanisms & novel therapeutics - CVGen mech2ther, AP.TEM

Abstract

Acute Myocardial Infarction (AMI) is defined as ischemic injury that causes cardiomyocytes death. Because the adult heart does not display regenerative capacity, endogenous cardiomyocytes renewal is limited so tissues repair after injury is compromised. Several studies have considered Adipose tissue Stromal Cells (ASC) in an attempt to repair damage to the infarcted myocardium. These studies have shown that transplantation of ASCs generally reduces infarct size, improves left ventricular injection fraction, reduces cardiomyocyte apoptosis, increases vascular density and myocardial perfusion. However, studies in rodents and pigs showed that even through intramyocardial injection only a small amount of transplanted ASCs were able to engraft and survive four weeks after injection, suggesting that ASCs have a pleiotropic effect. This paracrine action of the MSCs may be mediated by the exosomes, vesicles that have a diameter between 30-100nm and are secreted by several cell types. The function of the exosomes seems to be related to the extracellular communication, once they carry and transfer diverse components like cytokines, proteins, lipids, mRNA and microRNAs (miRNAs) to other cells. For this purpose, the aim of this work is to evaluate whether mesenchymal stem cells-derived exosomes are associated with cardioprotective effects by injection of these cells into post-myocardial infarction and elucidate the mechanisms responsible for these beneficial effects since they have not yet been clearly elucidated. (AU)