Cardiologia Traslazionale - Gruppo di Ricerca

1) Cardiac disease modeling and drug testing using iPSC technology. Cardiomyocytes (CM) derived from patient’s induced pluripotent stem cells (iPSCs) faithfully summarize ‘patient on a plate’ (individual level) and ‘clinical trial on a plate’ (population level) conditions. We use this technology for the implementation of Precision Medicine approaches, particularly for disease modeling and treatment. 

2) Cell therapy for cardiovascular diseases. We demonstrated that the beneficial effects exerted by mesenchymal stromal cells (MSCs) on ischemic hearts are mediated by their secretome and that MSCs of fetal origin (F-MSCs) are more effective than adult MSCs. Accordingly, we are developing clinical-grade protocols to scale up the production of F-MSC and their secretome. The ambitious goal is to implement therapies based on the use of secretome or microvesicles or single factors produced by F-MSCs for the treatment of ischemic heart disease, heart failure and other cardiac diseases.

3) Acute myocardial infarction registry. More than 15 years ago, we generated a registry comprising all patients admitted to our Cardiology Division with a diagnosis of acute ST-segment elevation myocardial infarction (STEMI). The database is updated regularly and includes patient follow-up. Several outcome studies have been conducted and published to date, and more will be performed to document how the treatment and clinical evolution of STEMI patients will evolve over time.

4) PREDESTINATION study. This is a multicenter, prospective, case-control study, of which our Unit is the lead partner. The study aims to identify the genetic and clinical causes underlying ventricular fibrillation events at the onset of a STEMI. To date, over 1500 patients have been enrolled.

1) Gnecchi M., Sala L., Schwartz P.J. Precision Medicine and cardiac channelopathies: when dreams meet reality. European Heart Journal, 2021;
2) Lee Y.K., Sala L., Mura M., Rocchetti M., Pedrazzini M., Ran X., Mak T.S.H., Crotti L., Sham P.C., Torre E., Zaza A., Schwartz P.J., Tse H.F., Gnecchi M. MTMR4 SNVs modulate ion channel degradation and clinical severity in congenital long QT syndrome: insights in the mechanism of action of protective modifier genes. Cardiovascular Research, 2021;
3) Mehta A., Ramachandra C.J.A., Singh P., Chitre A., Lua C.H., Mura M., Crotti L., Wong P., Schwartz P.J., Gnecchi M., Shim W. Identification of a targeted and testable antiarrhythmic therapy for long-QT syndrome type 2 using a patient-specific cellular model. European Heart Journal, 2018;
4) Ciuffreda M.C., Malpasso G., Chokoza C., Bezuidenhout D., Goetsch K.P., Mura M., Pisano F., Davies N.H., Gnecchi M. Synthetic extracellular matrix mimic hydrogel improves efficacy of mesenchymal stromal cell therapy for ischemic cardiomyopathy. Acta Biomaterialia, 2018;
5) Danieli P., Malpasso G., Ciuffreda M.C., Cervio E., Calvillo L., Copes F., Pisano F., Mura M., Kleijn L., de Boer R.A., Viarengo G., Rosti V., Spinillo A., Roccio M., Gnecchi M. Conditioned medium from human amniotic mesenchymal stromal cells limits infarct size and enhances angiogenesis. STEM CELLS Translational Medicine, 2015.

1) cell culture room with laminar hoods, CO2 incubators, light microscopes;
2) equipment for molecular biology analyses;
3) cloning equipment;
4) histology sample preparation (microtome and embedding station);
5) inverted fluorescent microscope and stereomicroscope with a wide array of filters.

Ricerca corrente projects n° 08064009, 08064017, 08064018 and 08064021. AIFA-TRS-2018-00001470.  Fondazione Cariplo No. 2019-1691. Leducq Foundation for Cardiovascular Research [18CVD05]. Progetto PRIN 2022 – 2022RZCWWH.

Fondazione Istituto Neurologico Mondino (Pavia), Istituto Auxologico Italiano IRCCS (Milan), Università di Milano-Bicocca, Università di Messina (Messina), ISMETT (Palermo), University of Cape Town (SA), Stanford University School of Medicine (USA), Center for iPS Cell Research and Application of Kyoto (Japan), Technion-Israel Institute of Technology (Israel), Vanderbilt Center for Arrhythmia Research and Therapeutics (USA).