Silvia Brunelli - Associate Professor
Department and institution: Department of Health Sciences, School of Medicine and Surgery, University of Milano Bicocca
tel. +39 02 64488308
institutional profile page: UNIMIB
see also: PubMed, BOA, ResearchGate, Scopus Author ID 7003321841
Keywords: Muscle regeneration, Tissue repair, Endothelial to Mesenchymal Transition, Endothelial Progenitors, Innate Immunity
Regeneration of muscle fibers, lost during pathological muscle degeneration or after injuries, is sustained by generation of new myofibers, Progenitors in the muscle comprise quiescent myogenic cells, the satellite cells, that are primary stem cells responsible for skeletal muscle regeneration after damage and vessel-associated progenitors, such as the mesoangioblasts (MAB). Using a genetic lineage tracing approach, a transgenic mouse expressing an inducible Cre under the control of an endothelial specific promoter we have provided new insights on the distinctive characteristics of the extraembryonic and embryonic hemogenic endothelium and we have identified for the first time the in vivo counterpart of embryonic MAB (Azzoni et al, 2014).
We also shown that macrophages are necessary for efficient vascular remodeling in the injured muscle. When phagocyte infiltration is compromised endothelial-derived progenitors undergo a significant endothelial to mesenchymal transition (EndoMT). This together with an inefficient tissue remodeling contributes to the accumulation of collagen, fat and significant fibrosis. Our findings provide new insights in EndoMT in the adult skeletal muscle, and suggest that endothelial cells in the skeletal muscle may represent a new target for therapeutic intervention in fibrotic diseases (Zordan et al, 2014). We are extending these studies to another diseases, both of genetic and acquired origin such as Fibrodysplasia Ossificans Progressive (FOP) (Cappato et al, High throughput screening for modulators of ACVR1 transcription potentially applicable to the treatment of Fibrodysplasia Ossificans Progressiva, in revision Disease and Models and Mechanisms) and Systemic Sclerosis (Nicolosi et al, 2016).
Main topics of the group
Molecular Mechanisms of Muscle regeneration, Endothelial to Mesenchymal Transition in Development and Diseases
Current research projects
- Fondazione Cariplo Ricerca Medica 2013 Role of cripto in orchestrating tissue remodelling in muscle damage. ordinator of the project (2 units) and Unit PI
- Italian Ministry of University PRIN 2012 Identificazione di nuove molecole terapeutiche per le malattie muscolari orfane su base infiammatoria. Unit PI
- Telethon GGP15196 New treatment strategies for Fibrodysplasia Ossificans Progressiva PI
Internal and external collaborators
1. Touvier T, De Palma C, Rigamonti E, Scagliola A, Incerti E, Mazelin L, Thomas JL, D'Antonio M, Politi L, Schaeffer L, Clementi E, Brunelli S. Muscle-specific Drp1 overexpression impairs skeletal muscle growth via translational attenuation. Cell Death Dis. 2015 Feb 26;6: e1663. doi: 10.1038/cddis.2014.595
2. Azzoni E, Conti V, Campana L, Dellavalle A, Adams RH, Cossu G and Brunelli S. Hemogenic endothelium generates mesoangioblasts that contribute to several mesodermal lineages in vivo (2014). Development 141:1821-1834;
3. Zordan, P, Rigamonti, E, Freudenberg, K, Conti, V, Azzoni, E, Patrizia Rovere-Querini, P, Brunelli, S. Macrophages commit postnatal endothelium derived-progenitors to angiogenesis and restrict endothelial to mesenchymal transition during muscle regeneration. (2014). Cell Death and Disease. Jan 30;5:e1031
4. Rigamonti E, Touvier T, Clementi E, Manfredi A, Brunelli S, Rovere-Querini P. Requirement of inducible Nitric Oxide Synthase for skeletal muscle regeneration after acute damage. Journal of Immunology (2013). 190(4):1767-77
5. Dellavalle A, Maroli G, Covarello D Azzoni E, Innocenzi A, Perani L, Antonini S, Sambasivan R, Brunelli S, Tajbakhsh S, Cossu G. (2011). Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells. Nature Communications. 2:499
Selected Recent Publications
Guardiola, O., Andolfi, G., Tirone, M., Iavarone, F., Brunelli, S., & Minchiotti, G. (2017).
Induction of Acute Skeletal Muscle Regeneration by Cardiotoxin Injection.
JOURNAL OF VISUALIZED EXPERIMENTS, 2017(119), 1-6. MORE
Tirone, M., Tran, N., Ceriotti, C., Gorzanelli, A., Canepari, M., Bottinelli, R., et al. (2017).
High mobility group box 1 orchestrates tissue regeneration via CXCR4.
JOURNAL OF EXPERIMENTAL MEDICINE, 215(1), 1-16. MORE
Cappato, S., Tonachini, L., Giacopelli, F., Tirone, M., Galietta, L., Sormani, M., et al. (2016).
High throughput screening for modulators of ACVR1 transcription potentially applicable to the treatment of Fibrodysplasia Ossificans Progressiva.
DISEASE MODELS & MECHANISMS. MORE
Nicolosi, P., Tombetti, E., Maugeri, N., Rovere-Querini, P., Brunelli, S., & Manfredi, A. (2016).
Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis.
STEM CELLS INTERNATIONAL, 2016, 1-12. MORE
Tirone, M., Conti, V., Manenti, F., Nicolosi, P., D'Orlando, C., Azzoni, E., et al. (2016).
Nitric Oxide Donor Molsidomine Positively Modulates Myogenic Differentiation of Embryonic Endothelial Progenitors.
PLOS ONE, 11(10). MORE