Staff:
- Alberto Crottogini, MD, PhD
- Luis Cuniberti, PhD
- Fernanda Daniela Olea, PhD
- Paola Locatelli, MD, PhD
- Anna Hnatiuk, MD, PhD
- Carlos Sebastián Giménez, MSc
Aims and scope:
The Cardiovascular Regeneration Laboratory aims at designing new therapeutic strategies based on gene therapy, stem cells and tissue engineering for cardiovascular diseases caused by tissue ischemia and/or loss of contractile cells.
We use porcine and ovine models of acute myocardial infarction, reperfused myocardial infarction, chronic myocardial ischemia, ischemic and non-ischemic heart failure and rabbit models of peripheral artery disease.
The reason for employing large mammals rather than mice and rats is to facilitate extrapolation of results to the human, thus highlighting the translational nature of our research.
Our early projects consisted of injecting a plasmid encoding VEGF165, that was later used in a clinical trial, and more recently of mesenchymal stem cells genetically modified to overexpress diverse growth factors. Other ongoing projects investigate the effect of bioresorbable scaffolds seeded with diaphragmatic myoblasts overexpressing connexin 43 on sheep with myocardial infarction and ventricular remodeling, and the effect of the HMGB1 protein in the same model. We have recently started a project aimed at inducing myocardial self-regeneration in sheep by manipulating the adult cardiomyocyte cell cycle with sequences selected from the transcriptome of phoetal, non-postmitotic cardiomyocytes.
International cooperations: Heart Institute (InCor), University of São Paulo, Brazil; Stanford Cardiovascular Institute, Stanford University, USA; Miami University Miller School of Medicine, USA; Istituto Dermopatico dell’Immacolata, Rome, Italy.
Selected publications:
1. Hnatiuk A, Ong S-G, Olea FD, Locatelli P, Riegler J, Lee W-H, Jen CH, De Lorenzi A, Giménez CS, Laguens R, Wu JC, Crottogini A.
Allogeneic mesenchymal stromal cells overexpressing mutant human HIF1-α in an ovine model of acute myocardial infarction. Journal of the American Heart Association 2016; 5(7). pii: e003714.
2. Locatelli P, Olea FD, Hnatiuk A, De Lorenzi A, Cerdá M, Giménez CS, Sepúlveda D, Laguens R, Crottogini A.
Mesenchymal Stromal Cells Overexpressing Vascular Endothelial Growth Factor in Ovine Myocardial Infarction. Gene Therapy 2015; 22: 449-457.
3. Olea FD, Locatelli P, Hnatiuk A, De Lorenzi A, Valdivieso L, Rocha E, RamÃrez R, Laguens R, Crottogini A.
Vascular endothelial growth factor overexpression does not enhance adipose stromal cells-induced protection on muscle damage in critical limb ischemia. Arterioslerosis, Thrombosis and Vascular Biology 35: 184-188, 2015.
4. Favaloro L, Diez M, Mendiz O, Vera Janavel G, Valdivieso L, Ratto R, Garelli G, Salmo F, Criscuolo M, Bercovich A, Crottogini A.
High-dose plasmid-mediated VEGF gene transfer is safe in patients with severe ischemic heart disease (GENESIS-I). A phase I, open-label, two years follow-up trial. Catheterization and Cardiovascular Interventions 82: 899-906, 2013.
5. Vera Janavel G, De Lorenzi A, Cortés C, Olea FD, Cabeza Meckert P, Bercovich A, Criscuolo M, Laguens R, Crottogini A.
Effect of VEGF gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after two months of coronary artery occlusion. Journal of Gene Medicine 14: 279-287, 2012.
6. Vera Janavel G, Crottogini A, Cabeza Meckert P, Cuniberti L, Mele A, Papouchado M, Fernández N, Bercovich A, Criscuolo M, Melo C, Laguens R.
Plasmid-mediated VEGF gene transfer induces cardiomyogenesis and reduces myocardial infarct size in sheep. Gene Therapy 13: 1133-1142, 2006.
7. Laguens R, Cabeza Meckert P, Vera Janavel G, De Lorenzi A, Lascano E, Negroni J, del Valle H, Cuniberti L, MartÃnez V, Dulbecco E, Melo C, Fernández N, Criscuolo M, Crottogini A.
Cardiomyocyte hyperplasia after plasmid-mediated vascular endothelial growth factor gene transfer in pigs with chronic myocardial ischemia. Journal of Gene Medicine 6: 222-227, 2004.
