Muscle functional recovery is driven by extracellular vesicles combined with muscle extracellular matrix in a volumetric muscle loss murine model.

Autor: Magarotto F; Stem Cells and Regenerative Medicine Lab, Institute of Pediatric Research Città Della Speranza, Padova, Italy; Department of Women and Children Health, University of Padova, Italy., Sgrò A; Department of Women and Children Health, University of Padova, Italy., Dorigo Hochuli AH; Pontificial University of Paraná, Brazil., Andreetta M; Department of Women and Children Health, University of Padova, Italy., Grassi M; Department of Women and Children Health, University of Padova, Italy., Saggioro M; Stem Cells and Regenerative Medicine Lab, Institute of Pediatric Research Città Della Speranza, Padova, Italy; Department of Women and Children Health, University of Padova, Italy., Nogara L; Biomedical Sciences Department, University of Padova, Italy; Venetian Institute of Molecular Medicine (VIMM), Padova, Italy., Tolomeo AM; Department of Women and Children Health, University of Padova, Italy; L.i.f.e.L.a.b. Program, Consorzio per La Ricerca Sanitaria (CORIS), Veneto Region, Padova, Italy., Francescato R; Stem Cells and Regenerative Medicine Lab, Institute of Pediatric Research Città Della Speranza, Padova, Italy., Collino F; Laboratory of Translational Research in Paediatric Nephro-urology, Fondazione Ca' Granada IRCCS Ospedale Maggiore Policlinico, Milano, Italy., Germano G; Institute of Pediatric Research Città Della Speranza, Padova, Italy., Caicci F; Department of Biology, University of Padua, Italy., Maghin E; Department of Women and Children Health, University of Padova, Italy; Tissue Engineering Lab, Institute of Pediatric Research Città Della Speranza, Padova, Italy., Piccoli M; Tissue Engineering Lab, Institute of Pediatric Research Città Della Speranza, Padova, Italy., Jurga M; The Cell Factory BVBA (Esperite NV), Italy., Blaauw B; Biomedical Sciences Department, University of Padova, Italy; Venetian Institute of Molecular Medicine (VIMM), Padova, Italy., Gamba P; Department of Women and Children Health, University of Padova, Italy., Muraca M; Department of Women and Children Health, University of Padova, Italy; Institute of Pediatric Research Città Della Speranza, Padova, Italy; L.i.f.e.L.a.b. Program, Consorzio per La Ricerca Sanitaria (CORIS), Veneto Region, Padova, Italy., Pozzobon M; Stem Cells and Regenerative Medicine Lab, Institute of Pediatric Research Città Della Speranza, Padova, Italy; Department of Women and Children Health, University of Padova, Italy. Electronic address: michela.pozzobon@unipd.it.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2021 Feb; Vol. 269, pp. 120653. Date of Electronic Publication: 2021 Jan 07.
DOI: 10.1016/j.biomaterials.2021.120653
Abstrakt: 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.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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