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RESEARCH AREA AND TRANSLATIONAL RESEARCH
EXTRACELLULAR VESICLES

Therapeutic role in cardiovascular disease: CMC has investigated the biological role and the therapeutic potential of secreted extracellular vesicles (EV), particularly of nanosized vesicles of endosomal origin called exosomes, in cardiovascular diseases, with a focus on acute myocardial infarction. Studies from the lab showed that EV secreted by human cardiac mesenchymal-derived progenitor cells were endowed with beneficial biological activities, as demonstrated in both in vitro and in vivo myocardial infarction models and chemotherapy-induced cardiotoxicity models. These properties included cytoprotective, pro-angiogenic, anti-fibrotic, and pro-proliferative effects in cardiomyocytes. In collaboration with the Department of Heart Surgery at Zurich University Hospital, we also demonstrated that such EV significantly reduced infarct scar in a preclinical model of acute myocardial infarction in pigs.

Physio-pathological role in cardiovascular system: CMC is actively studying the role of miRNA carried by cardiomyocyte derived-extracellular vesicles in heart development. Particularly, we aim to understand the physiological signaling that unlock cardiomyocyte proliferation to the development of new therapeutic strategy in myocardial regeneration.

RESEARCH METHODS

CMC has a major expertise in extracellular vesicles (EV) isolation and characterization. EV from cell culture or biological fluid are isolated using various protocols including ultracentrifugation, density gradient ultracentrifugation, immunobeads, and size exclusion chromatography (SEC). Extracellular vesicles are characterized by Nanoparticle Tracking Analysis (NTA), flow cytometry, western blot, RealTime-PCR analysis and electron microscopy.

Functional analysis of EV are then evaluated in vitro and vivo models. In vitro EV are tested on cardiomyocyte (from neonatal mouse or human iPS-derived), cardiac fibroblast (mouse and human) and on a human heart organoid (iPS-derived cardiomyocyte and cardiac fibroblast). The use of 3D culture is a cutting edge technique that allow to perform experiments taking into account the synergistic effect of cardiac cells under different stimuli.

In vivo acute myocardial infarct models were used for studying the effects of human cardiac mesenchymal-derived progenitor cells on ischemic cardiac injury. An in vivo model of chemotherapy-induced cardiotoxicity was also developed.

GROUP LEADER
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Prof. Giuseppe Vassalli, MD

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BRIEF CV

Prof. Giuseppe Vassalli, Group Leader of the Molecular and Cellular Cardiology Laboratory at the Istituto Cardiocentro Ticino, is a scientist and a clinical cardiologist. He received his MD degree from the University of Berne and his cardiological training at the University of Zurich. He then completed a 3-year research fellowship in cardiovascular biology at University of Chicago and at Gladstone Institute of Cardiovascular Diseases at University of California (San Francisco). Next, he was the director of the Molecular Cardiology Laboratory at CHUV Medical Center (Lausanne). Over the past 12 years, he worked as Head of the Laboratory of Cellular and Molecular Cardiology at Istituto Cardiocentro Ticino (Lugano) while also working as a senior cardiologist at this institution. His research activity involved three areas of investigation: the role of extracellular vesicles in cardiovascular diseases, induced pluripotent stem (iPS) cell-derived cardiomyocytes, and cellular cardiac electrophysiology. A recent basic research study from the group showed that human cardiac-derived stromal progenitor cells secreted extracellular vesicles enriched with periostin, which stimulated cardiomyocyte proliferation. A recent clinical study by the group showed that serum extracellular vesicles in patients after acute myocardial infarction were of diagnostic interest. Prof. Vassalli was assistant professor at the University of Lausanne from 2000 to 2006, assistant professor sponsored by the Swiss National Science Foundation from 2006 to 2012, and associate professor at the University of Lausanne from 2012 to 2017. He then became associate professor at University of Zurich in 2017, and associate professor at USI in 2019.
RESEARCHERS
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Dr. Carolina Balbi

EXTERNAL COLLABORATOR

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Sara Bolis

LAB MANAGER
PLURIPOTENT STEM CELL CULTURE

FORMER LAB MEMBERS

  • Veronica Lisi (PhD Visiting student – Università degli studi di Roma “Foro Italico”)
  • Concetta Schiano (PhD Visiting researcher)
RECENT PUBLICATIONS

LIST OF PUBLICATIONS

  • Balbi C, Vassalli G.
    Exosomes: Beyond stem cells for cardiac protection and repair. Stem Cells.
    2020 Nov;38(11):1387-1399. doi: 10.1002/stem.3261. Epub 2020 Aug 28. Stem Cells. 2020. PMID: 32761640
  • Burrello J, Bolis S, Balbi C, Burrello A, Provasi E, Caporali E, Gauthier LG, Peirone A, D’Ascenzo F, Monticone S, Barile L, Vassalli G.
    An extracellular vesicle epitope profile is associated with acute myocardial infarction.
    J Cell Mol Med. 2020 Jul 14;24(17):9945-57. doi: 10.1111/jcmm.15594.
  • Pianezzi E, Altomare C, Bolis S, Balbi C, Torre T, Rinaldi A, Camici GG, Barile L, Vassalli G.
    Role of somatic cell sources in the maturation degree of human induced pluripotent stem cell-derived cardiomyocytes.
    Biochim Biophys Acta Mol Cell Res. 2020 Mar;1867(3):118538. doi: 10.1016/j.bbamcr.2019.118538. Epub 2019 Aug 28.Biochim Biophys Acta Mol Cell Res. 2020. PMID: 31472168
  • Milano G, Biemmi V, Lazzarini E, Balbi C, Ciullo A, Bolis S, Ameri P, Di Silvestre D, Mauri P, Barile L, Vassalli G.
    Intravenous administration of cardiac progenitor cell-derived exosomes protects against doxorubicin/trastuzumab-induced cardiac toxicity.
    Cardiovasc Res. 2020 Feb 1;116(2):383-392. doi: 10.1093/cvr/cvz108.Cardiovasc Res. 2020. PMID: 31098627.
  • Balbi C, Milano G, Fertig TE, Lazzarini E, Bolis S, Taniyama Y, Sanada F, Di Silvestre D, Mauri P, Gherghiceanu M, Lüscher TF, Barile L, Vassalli G.
    An exosomal-carried short periostin isoform induces cardiomyocyte proliferation.
    Theranostics. 2021 Mar 23;11(12):5634-5649. doi: 10.7150/thno.57243. eCollection 2021.Theranostics. 2021. PMID: 33897872.
  • Altomare C, Lodrini AM, Milano G, Biemmi V, Lazzarini E, Bolis S, Pernigoni N, Torre E, Arici M, Ferrandi M, Barile L, Rocchetti M, Vassalli G.
    Structural and electrophysiological changes in a model of cardiotoxicity induced by anthracycline combined with trastuzumab.
    Front Physiol. 2021 Apr 7;12:658790. doi: 10.3389/fphys.2021.658790. eCollection 2021.
  • Balbi C, Burrello J, Bolis S, Lazzarini E, Biemmi V, Pianezzi E, Burrello A, Caporali E, Grazioli LG, Martinetti G, Fusi-Schmidhauser T, Vassalli G, Melli G, Barile L.
    Circulating extracellular vesicles are endowed with enhanced procoagulant activity in SARS-CoV-2 infection.
    EBioMedicine. 2021 May;67:103369. doi: 10.1016/j.ebiom.2021.103369. Epub 2021 May 7.EBioMedicine. 2021. PMID: 33971404

PUBLICATIONS IN COLLABORATIONS WITH OTHER GROUPS
  • Biemmi V, Milano G, Ciullo A, Cervio E, Burrello J, Dei Cas M, Paroni R, Tallone T, Moccetti T, Pedrazzini G, Longnus S, Vassalli G, Barile L.
    Inflammatory extracellular vesicles prompt heart dysfunction via TRL4-dependent NF-κB activation.
    Theranostics. 2020 Feb 3;10(6):2773-2790. doi: 10.7150/thno.39072. eCollection 2020.PMID: 32194834.
  • Burrello J, Biemmi V, Dei Cas M, Amongero M, Bolis S, Lazzarini E, Bollini S, Vassalli G, Paroni R, Barile L.
    Sphingolipid composition of circulating extracellular vesicles after myocardial ischemia.
    Sci Rep. 2020 Sep 30;10(1):16182. doi: 10.1038/s41598-020-73411-7.
  • Vacchi E, Burrello J, Di Silvestre D, Burrello A, Bolis S, Mauri P, Vassalli G, Cereda CW, Farina C, Barile L, Kaelin-Lang A, Melli G.
    Immune profiling of plasma-derived extracellular vesicles identifies Parkinson disease.
    Neurol Neuroimmunol Neuroinflamm. 2020 Aug 12;7(6):e866. doi: 10.1212/NXI.0000000000000866.
  • Castellani C, Burrello J, Fedrigo M, Burrello A, Bolis S, Di Silvestre D, Tona F, Bottio T, Biemmi V, Toscano G, Gerosa G, Thiene G, Basso C, Longnus SL, Vassalli G, Angelini A, Barile L.
    Circulating extracellular vesicles as non-invasive biomarker of rejection in heart transplant.
    J Heart Lung Transplant. 2020 Oct;39(10):1136-1148. doi: 10.1016/j.healun.2020.06.011.
  • Balbi C, Burrello J, Bolis S, Lazzarini E, Biemmi V, Pianezzi E, Burrello A, Caporali E, Grazioli LG, Martinetti G, Fusi-Schmidhauser T, Vassalli G, Melli G, Barile L.
    Circulating extracellular vesicles are endowed with enhanced procoagulant activity in SARS-CoV-2 infection.
    EBioMedicine. 2021 May;67:103369. doi: 10.1016/j.ebiom.2021.103369. Epub 2021 May 7.PMID: 33971404
  • Burrello J, Bianco G, Burrello A, Manno C, Maulucci F, Pileggi M, Nannoni S, Michel P, Bolis S, Melli G, Vassalli G, Albers GW, Cianfoni A, Barile L, Cereda CW.
    Extracellular Vesicle Surface Markers as a Diagnostic Tool in Transient Ischemic Attacks.
    Stroke. 2021 Aug 4:STROKEAHA120033170. doi: 10.1161/STROKEAHA.120.033170.
  • Burrello J, Tetti M, Forestiero V, Biemmi V, Bolis S, Pomatto MAC, Amongero M, Di Silvestre D, Mauri P, Vassalli G, Camussi G, Williams TA, Mulatero P, Barile L, Monticone S.
    Characterization of Circulating Extracellular Vesicle Surface Antigens in Patients With Primary Aldosteronism.
    Hypertension. 2021 Sep;78(3):726-737. doi: 10.1161/HYPERTENSIONAHA.121.17136. Epub 2021 Jul 26.PMID: 34304584.
FUNDINGS

LIST OF FUNDINGS

  • 2022-01 to 2023-01 | Dr. Carolina Balbi: Swiss Heart Foundation (Bern, Switzerland) Grant_number: FF21017 Myocardial Infarction Adverse Remodeling: the Role of Circulating Extracellular Vesicles
  • 2021-06 to 2024-06 | Prof. Giuseppe Vassalli: Grant Fondazione Leonardo (Lugano, Switzerland) Cardiac regeneration via modulation of cardiomyocyte-secreted exosomes: Role of IL13
  • 2021-02 to 2022-08 | Prof. Giuseppe Vassalli: Innosuisse (Bern, Switzerland) Grant_number: 50961.1 IP-LS ExoFET: Portable medical device for the immobilization and detection of Exosomes in human serum based on junctionless field effect transistors (FETs)
  • 2017-09 to 2021-05 | Prof. Giuseppe Vassalli: Swiss National Science Foundation – SNF (Bern, Switzerland) GRANT_NUMBER: 169194 Cardioprotection by adult human cardiac progenitor cell-derived exosomes
PHOTOGALLERY