Extracellular vesicles and Duchenne muscular dystrophy pathology: Modulators of disease progression

Laura Yedigaryan; Maurilio Sampaolesi

doi:10.3389/fphys.2023.1130063

Extracellular vesicles and Duchenne muscular dystrophy pathology: Modulators of disease progression

Front Physiol. 2023 Feb 14:14:1130063. doi: 10.3389/fphys.2023.1130063. eCollection 2023.

Authors

Laura Yedigaryan¹, Maurilio Sampaolesi^{1

2}

Affiliations

¹ Translational Cardiomyology Laboratory, Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
² Histology and Medical Embryology Unit, Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Sapienza University of Rome, Rome, Italy.

Abstract

Duchenne muscular dystrophy (DMD) is a devastating disorder and is considered to be one of the worst forms of inherited muscular dystrophies. DMD occurs as a result of mutations in the dystrophin gene, leading to progressive muscle fiber degradation and weakness. Although DMD pathology has been studied for many years, there are aspects of disease pathogenesis and progression that have not been thoroughly explored yet. The underlying issue with this is that the development of further effective therapies becomes stalled. It is becoming more evident that extracellular vesicles (EVs) may contribute to DMD pathology. EVs are vesicles secreted by cells that exert a multitude of effects via their lipid, protein, and RNA cargo. EV cargo (especially microRNAs) is also said to be a good biomarker for identifying the status of specific pathological processes that occur in dystrophic muscle, such as fibrosis, degeneration, inflammation, adipogenic degeneration, and dilated cardiomyopathy. On the other hand, EVs are becoming more prominent vehicles for custom-engineered cargos. In this review, we will discuss the possible contribution of EVs to DMD pathology, their potential use as biomarkers, and the therapeutic efficacy of both, EV secretion inhibition and custom-engineered cargo delivery.

Keywords: cardiomyopathy; exosomes; extracellular vesicles (EVs); induced pluripotent stem cells (iPSCs); miRNAs; muscle regeneration; muscular dystrophies; satellite cells.

Publication types

Review

Grants and funding

The work done in the authors’ laboratory is supported by Small Research Infrastructure KU Leuven–BioAssemblyBot 400 (KA/20/088), Research Foundation Flanders (FWO) (#G066821N), INTERREG–Euregio Meuse-Rhine (GYM, Generate your muscle 2020-EMR116), and the Italian Ministry of Health, Ricerca Finalizzata (RF-2019-12369703). MS is a recipient of the Hercules Foundation grant (AKUL/19/34) for the financing provided to purchase the high throughput calcium imaging system.