Translational Cardiology - Massimiliano Gnecchi

Massimiliano Gnecchi, PI

Email: m.gnecchi@unipv.it

Phone: (+39) 0382 502482

Massimiliano Gnecchi, PI, Associate Professor

Manuela Mura, researcher

Francesca Bastaroli, postdoc fellow

Chiara Guarona, PhD student

Sara Montanaro, postgraduate fellow

Francesca Misitano, postgraduate fellow

In our laboratory we carry out basic and translational research with the ultimate goal of discovering new cellular and molecular therapies and identifying precision medicine approaches to improve the care of heart patients.

In particular, the main lines of research are the following:

1. Cardiac disease modeling using iPSC technology. Starting from somatic cells isolated from patients, we are able to obtain cardiomyocytes (CM) derived from the iPSCs (iPSC-CMs) of the same subjects in just a few weeks. We have already proved that patient-specific iPSC-CMs recapitulate the abnormal cardiac phenotype of hereditary cardiac arrhythmias and can be used to test antiarrhythmic drugs. iPSC-CMs faithfully summarize ‘patient on a plate’ (individual level) and ‘clinical trial on a plate’ (population level) conditions. Thus, we are exploiting this technology for the implementation of Precision Medicine approaches for disease treatment and prevention that take into account individual genetic and phenotypic variability, allowing the identification of targeted diagnostic and therapeutic strategies.
2. Cell therapy for critically ill cardiovascular patients. We demonstrated that MSC-mediated beneficial effects on infarcted hearts are mainly mediated by their secretome, and that mesenchymal stem cells of fetal origin isolated from human placenta (F-MSC) are more effective than adult MSC of bone marrow origin that, over the years, tend to lose therapeutic power due to aging and depletion of many paracrine factors. We are now developing a clinical grade protocol for scaling up the production of F-MSC and what they produce. The ambitious goal is to develop therapies based on the use of secretome or microvesicles produced by F-MSC to treat myocardial infarction, heart failure and pulmonary hypertension. Another interest of group is represented by the identification of risk factors and biomarkers that can help stratifying the individual cardiovascular risk.

Gnecchi M, Sala L, Schwartz PJ. Precision Medicine and cardiac channelopathies: when dreams meet reality. Eur Heart J. 2021 May 1;42(17):1661-1675. doi: 10.1093/eurheartj/ehab007.

Lee YK, Sala L, Mura M, Rocchetti M, Pedrazzini M, Ran X, Mak TSH, Crotti L, Sham PC, Torre E, Zaza A, Schwartz PJ, Tse HF, 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. Cardiovasc Res. 2021 Feb 22;117(3):767-779. doi: 10.1093/cvr/cvaa019.

Mehta A, Ramachandra CJA, Singh P, Chitre A, Lua CH, Mura M, Crotti L, Wong P, Schwartz PJ, Gnecchi M, Shim W. Identification of a targeted and testable antiarrhythmic therapy for long-QT syndrome type 2 using a patient-specific cellular model. Eur Heart J. 2018 Apr 21;39(16):1446-1455. doi: 10.1093/eurheartj/ehx394.

Ciuffreda MC, Malpasso G, Chokoza C, Bezuidenhout D, Goetsch KP, Mura M, Pisano F, Davies NH, Gnecchi M. Synthetic extracellular matrix mimic hydrogel improves efficacy of mesenchymal stromal cell therapy for ischemic cardiomyopathy. Acta Biomater. 2018 Apr 1;70:71-83. doi: 10.1016/j.actbio.2018.01.005.

Danieli P, Malpasso G, Ciuffreda MC, Cervio E, Calvillo L, Copes F, Pisano F, Mura M, Kleijn L, de Boer RA, 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 Transl Med. 2015 May;4(5):448-58. doi: 10.5966/sctm.2014-0253.