Additive effect of transplantation of adult stem cells post-infarction on the cardiac perfusion in pigs treated with beta-blocker and angiotensin-converting enzyme inhibitor

Abstract

Cardiovascular diseases such as myocardial infarction are the leading cause of death in the world population. The current therapeutic strategies used for the treatment of these diseases do not benefit all types of patient. Thus it is necessary to develop alternative therapeutic strategies that add up to well-established therapies.In this sense, the use of stem cells as a source of heart cells is shown as a promising approach in the context of tissue regeneration. Stem cells from different sources used in preclinical studies have shown potential to improve ventricular function after injury. A large body of evidence suggests that the mechanisms of action of stem cells are poorly linked to transdifferentiation and tissue replacement. The predominant mechanisms of the transplanted cells would be linked to paracrine release of bioactive molecules important in the context of post-infarct heart repair.Substantial evidence shows that stem cells from different sources can secrete important factors for heart repair after injury. A range of cytokines and pro-angiogenic, anti-apoptotic and cell proliferation proteins were described present in the culture medium of these cells. In our laboratory we also evaluated the secretory behavior of stem cells from adipose tissue subjected to physical and chemical stimuli and observe a large amount of secreted bioactive molecules that may play an important role in the process of post-infarct heart repair. Among these molecules stands VEGF, a cytokine involved in crucial processes of repair heart, whose modulation strikingly affects the formation of new blood vessels resulting in impaired cardiac function.This proposal is based on observations of our group and others that the transplantation of mesenchymal cells in rodents is beneficial and aims to assess the potential of cell therapy with pASCs or conditioned medium in pigs subjected to myocardial infarction, whereas this model is most relevant to transpose possible results to the clinic. The experimental pig model mimics important morphological and functional characteristics of the human heart. In addition, the efficacy of cell transplantation after myocardial infarction will be checked in the presence of inhibition of angiotensin-converting enzyme, which is a set of therapies in clinical practice.