TY - JOUR
T1 - Muscle functional recovery is driven by extracellular vesicles combined with muscle extracellular matrix in a volumetric muscle loss murine model
AU - Magarotto, Fabio
AU - Sgrò, Alberto
AU - Dorigo Hochuli, Agner Henrique
AU - Andreetta, Marina
AU - Grassi, Michele
AU - Saggioro, Mattia
AU - Nogara, Leonardo
AU - Tolomeo, Anna Maria
AU - Francescato, Riccardo
AU - Collino, Federica
AU - Germano, Giuseppe
AU - Caicci, Federico
AU - Maghin, Edoardo
AU - Piccoli, Martina
AU - Jurga, Marcin
AU - Blaauw, Bert
AU - Gamba, Piergiorgio
AU - Muraca, Maurizio
AU - Pozzobon, Michela
N1 - Funding Information:
This work has been supported by Synergy project 19/01, Institute of Pediatric Research Città della Speranza and by Associazione Puzzle, Padova, Italy. MP was funded by University of Padova, Assegno di Ricerca di tipo A. This work contributes to the COST Action CA17116 “International Network for Translating Research on Perinatal Derivatives into Therapeutic Approaches (SPRINT),” supported by COST ( European Cooperation in Science and Technology ).
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/2
Y1 - 2021/2
N2 - Biological scaffolds derived from decellularized tissues are being investigated as a promising approach to repair volumetric muscle losses (VML). Indeed, extracellular matrix (ECM) from decellularized tissues is highly biocompatible and mimics the original tissue. However, the development of fibrosis and the muscle stiffness still represents a major problem. Intercellular signals mediating tissue repair are conveyed via extracellular vesicles (EVs), biologically active nanoparticles secreted by the cells. This work aimed at using muscle ECM and human EVs derived from Wharton Jelly mesenchymal stromal cells (MSC EVs) to boost tissue regeneration in a VML murine model. Mice transplanted with muscle ECM and treated with PBS or MSC EVs were analyzed after 7 and 30 days. Flow cytometry, tissue analysis, qRT-PCR and physiology test were performed. We demonstrated that angiogenesis and myogenesis were enhanced while fibrosis was reduced after EV treatment. Moreover, the inflammation was directed toward tissue repair. M2-like, pro-regenerative macrophages were significantly increased in the MSC EVs treated group compared to control. Strikingly, the histological improvements were associated with enhanced functional recovery. These results suggest that human MSC EVs can be a naturally-derived boost able to ameliorate the efficacy of tissue-specific ECM in muscle regeneration up to the restored tissue function.
AB - Biological scaffolds derived from decellularized tissues are being investigated as a promising approach to repair volumetric muscle losses (VML). Indeed, extracellular matrix (ECM) from decellularized tissues is highly biocompatible and mimics the original tissue. However, the development of fibrosis and the muscle stiffness still represents a major problem. Intercellular signals mediating tissue repair are conveyed via extracellular vesicles (EVs), biologically active nanoparticles secreted by the cells. This work aimed at using muscle ECM and human EVs derived from Wharton Jelly mesenchymal stromal cells (MSC EVs) to boost tissue regeneration in a VML murine model. Mice transplanted with muscle ECM and treated with PBS or MSC EVs were analyzed after 7 and 30 days. Flow cytometry, tissue analysis, qRT-PCR and physiology test were performed. We demonstrated that angiogenesis and myogenesis were enhanced while fibrosis was reduced after EV treatment. Moreover, the inflammation was directed toward tissue repair. M2-like, pro-regenerative macrophages were significantly increased in the MSC EVs treated group compared to control. Strikingly, the histological improvements were associated with enhanced functional recovery. These results suggest that human MSC EVs can be a naturally-derived boost able to ameliorate the efficacy of tissue-specific ECM in muscle regeneration up to the restored tissue function.
KW - Extracellular matrix
KW - Extracellular vesicles
KW - Functional tissue regeneration
KW - Volumetric muscle loss
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U2 - 10.1016/j.biomaterials.2021.120653
DO - 10.1016/j.biomaterials.2021.120653
M3 - Article
C2 - 33461058
AN - SCOPUS:85099343290
VL - 269
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
M1 - 120653
ER -