Directors: Alberto Crottogini, MD, PhD and Luis Cuniberti, PhD
Research team: Daniela Olea, PhD, Paola Locatelli, MD, PhD, Sebastián Giménez, PhD, María del Rosario Bauzá, MSc, Giovanna Castillo Velásquez, MSc, Ayelén López, Msc, Cristian Núñez Pedroso, Msc.
Cardiovascular diseases are the main cause of mortality worldwide. Of them, ischemic heart disease (IHD) leads the ranking, with 31% mortality rate in Argentina and in the world. Its most severe complication is acute myocardial infarction and its consequence, heart failure. The main goal of our lab is promoting myocardial regeneration as a means to attenuate the consequences of IHD. We also aim at inducing vascular growth in peripheral artery disease (PAD), a progressive, invalidating ailment often leading to amputation and for which no effective treatment exists. To these ends, we have designed and validated large mammalian models of IHD and rabbit models of PAD. The regenerative strategies that we use include the transfer of genes encoding mitogenic proteins, the implant of genetically modifies stem cells and the implant of bio-resorbable scaffolds seeded with stem cells of diverse origins and differentiation potential. More recently, we have launched a line of research directed to disclose positive and negative regulators of the cardiomyocyte cell cycle that could eventually be targeted to induce the adult cardiomyocyte to reenter the cell cycle and advance into cytokinesis. This approach would assure the inter-cell electromechanical connection needed for physiological sincityal function, a fact not yet convincingly demonstrated with stem cell therapy.
A key objective of our lab is to imprint a translational profile to our pre-clinical scientific and technological developments, designing and conducting safety and efficacy clinical trials in patients of our University hospital, as we have already done with a plasmid encoding human VEGF in patients with severe, symptomatic IHD not amenable for conventional revascularization.
Present lines of investigation:
Implant of Muse cells overexpressing a mutant, oxygen resistant HIF1α in a sheep model of acute myocardial infarction.
Cardiomyocyte proliferation by transfer of pro-mitotic genes and miRNA-mediated silencing of cell cycle inhibitory genes in rats and sheep with myocardial infarction.
Gene and cell therapy to induce angio-arteriogenesis and muscle regeneration in rabbits with peripheral artery disease.
Bioinformatic analysis of the cardiomyocyte transcriptome at diverse stages of development to identify novel targets for therapeutic heart regeneration.
Biomaterials for stem cell delivery in myocardial regeneration.