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

Fabio Magarotto, Alberto Sgrò, Agner Henrique Dorigo Hochuli, Marina Andreetta, Michele Grassi, Mattia Saggioro, Leonardo Nogara, Anna Maria Tolomeo, Riccardo Francescato, Federica Collino, Giuseppe Germano, Federico Caicci, Edoardo Maghin, Martina Piccoli, Marcin Jurga, Bert Blaauw, Piergiorgio Gamba, Maurizio Muraca, Michela Pozzobon

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number120653
JournalBiomaterials
Volume269
DOIs
Publication statusPublished - Feb 2021

Keywords

  • Extracellular matrix
  • Extracellular vesicles
  • Functional tissue regeneration
  • Volumetric muscle loss

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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