Exosome-mediated improvement in membrane integrity and muscle function in dystrophic mice

Leng, Ling; Dong, Xue; Gao, Xianjun; Ran, Ning; Geng, Mengyuan; Zuo, Bingfeng; Wu, Yingjie; Li, Wei; Yan, Hua; Hou, Gang; Yin, HaiFang

doi:10.1016/j.ymthe.2020.12.018

Cited by 21 publications

(12 citation statements)

References 58 publications

(64 reference statements)

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“…Duchenne muscular dystrophy (DMD) is a life-threatening disorder that is caused by the absence of functional dystrophin protein, resulting cell membrane fragility, muscle damage, inflammation, fibrosis, and ultimate degeneration [ 191 , 192 ]. EVs from cardiosphere-derived cells (CDCs) were reported to be a therapeutic candidate for DMD; notably, the obtaining of CDCs is time-consuming and highly technical for isolation and purification maintenance [ 193 ]. Systemic administration of EVs derived from hMSCs, murine serum, and myotubes can delay pathological progression via improving membrane integrity in mdx mice without detectable toxicity [ 193 ].…”

Section: Musculoskeletal Diseasesmentioning

confidence: 99%

“…EVs from cardiosphere-derived cells (CDCs) were reported to be a therapeutic candidate for DMD; notably, the obtaining of CDCs is time-consuming and highly technical for isolation and purification maintenance [ 193 ]. Systemic administration of EVs derived from hMSCs, murine serum, and myotubes can delay pathological progression via improving membrane integrity in mdx mice without detectable toxicity [ 193 ]. However, these approaches were unable to achieve cure effects for DMD.…”

Section: Musculoskeletal Diseasesmentioning

confidence: 99%

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Tailored Extracellular Vesicles: Novel Tool for Tissue Regeneration

Qian

et al. 2022

Stem Cells International

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Extracellular vesicles (EVs) play an essential part in multiple pathophysiological processes including tissue injury and regeneration because of their inherent characteristics of small size, low immunogenicity and toxicity, and capability of carrying a variety of bioactive molecules and mediating intercellular communication. Nevertheless, accumulating studies have shown that the application of EVs faces many challenges such as insufficient therapeutic efficacy, a lack of targeting capability, low yield, and rapid clearance from the body. It is known that EVs can be engineered, modified, and designed to encapsulate therapeutic cargos like proteins, peptides, nucleic acids, and drugs to improve their therapeutic efficacy. Targeted peptides, antibodies, aptamers, magnetic nanoparticles, and proteins are introduced to modify various cell-derived EVs for increasing targeting ability. In addition, extracellular vesicle mimetics (EMs) and self-assembly EV-mimicking nanocomplex are applied to improve production and simplify EV purification process. The combination of EVs with biomaterials like hydrogel, and scaffolds dressing endows EVs with long-term therapeutic efficacy and synergistically enhanced regenerative outcome. Thus, we will summarize recent developments of EV modification strategies for more extraordinary regenerative effect in various tissue injury repair. Subsequently, opportunities and challenges of promoting the clinical application of engineered EVs will be discussed.

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Section: Musculoskeletal Diseasesmentioning

confidence: 99%

Section: Musculoskeletal Diseasesmentioning

confidence: 99%

Tailored Extracellular Vesicles: Novel Tool for Tissue Regeneration

Qian

et al. 2022

Stem Cells International

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“…This activation then induces antioxidant response element-controlled genes and decreases the expression of inflammatory genes, including vascular cell adhesion molecule 1, intercellular adhesion molecule 1, monocyte chemoattractant protein-1, IL-1β, IL-6, and TNF-α, by inhibiting NF-κB activation in macrophages and endothelial cells, ultimately leading to suppression of the recruitment of monocytes to the endothelium and macrophage M1 differentiation [152]. Furthermore, nSMase2/Smpd3 acts upstream of mitogen-activated protein kinase and NF-κB signaling pathways of TNF-α mediated inflammatory responses in monocytic cells/macrophages [153].…”

Section: Neutral Sphingomyelinase 2/sphingomyelin Phosphodiesterase 3 (Nsmase2/smpd3) and Dmdmentioning

confidence: 99%

Therapeutic Application of Extracellular Vesicles-Capsulated Adeno-Associated Virus Vector via nSMase2/Smpd3, Satellite, and Immune Cells in Duchenne Muscular Dystrophy

Matsuzaka

Hirai

Hashido

et al. 2022

IJMS

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Duchenne muscular dystrophy (DMD) is caused by loss-of-function mutations in the dystrophin gene on chromosome Xp21. Disruption of the dystrophin–glycoprotein complex (DGC) on the cell membrane causes cytosolic Ca2+ influx, resulting in protease activation, mitochondrial dysfunction, and progressive myofiber degeneration, leading to muscle wasting and fragility. In addition to the function of dystrophin in the structural integrity of myofibers, a novel function of asymmetric cell division in muscular stem cells (satellite cells) has been reported. Therefore, it has been suggested that myofiber instability may not be the only cause of dystrophic degeneration, but rather that the phenotype might be caused by multiple factors, including stem cell and myofiber functions. Furthermore, it has been focused functional regulation of satellite cells by intracellular communication of extracellular vesicles (EVs) in DMD pathology. Recently, a novel molecular mechanism of DMD pathogenesis—circulating RNA molecules—has been revealed through the study of target pathways modulated by the Neutral sphingomyelinase2/Neutral sphingomyelinase3 (nSMase2/Smpd3) protein. In addition, adeno-associated virus (AAV) has been clinically applied for DMD therapy owing to the safety and long-term expression of transduction genes. Furthermore, the EV-capsulated AAV vector (EV-AAV) has been shown to be a useful tool for the intervention of DMD, because of the high efficacy of the transgene and avoidance of neutralizing antibodies. Thus, we review application of AAV and EV-AAV vectors for DMD as novel therapeutic strategy.

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“…In all of these studies, the investigated EVs were found to contain proregenerative cargo including proteins and miRNAs. 14,15,28 More recently, Leng et al 31 compared the benefits of systemic administration of MSC-derived EVs, serumderived EVs, or myotube-derived EVs on muscle function in mice with the progressive muscle wasting disease, Duchenne muscular dystrophy (DMD). EVs from all 3 sources resulted in improved skeletal muscle function and myoarchitecture.…”

Section: Muscle Regenerationmentioning

confidence: 99%

Regenerative medicine 2.0: extracellular vesicle–based therapeutics for musculoskeletal tissue regeneration

Williams

Ehrhart

2022

javma

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In recent years, extracellular vesicles (EVs) have emerged as prominent mediators of the homeostasis, repair, and regeneration of musculoskeletal tissues including bone, skeletal muscle, and cartilage. Accordingly, the therapeutic potential of EVs for regenerative medicine applications has not gone unnoticed. The use of EVs for the treatment of musculoskeletal injury and disease in veterinary species is a nascent but rapidly expanding area of research. Recent studies in this area have demonstrated the safety and feasibility of EV products in dogs and horses. While early clinical responses to EV-based therapeutics in companion animals have been favorable, more rigorously designed, sufficiently powered, and placebo-controlled clinical trials are required to fully elucidate the clinical benefits and best-use scenarios for EV therapeutics in veterinary medicine. Additionally, clinical translation of EV-based therapeutics will require Good Manufacturing Practice–compliant methods to scale up and purify EV products. Despite these challenges, EVs hold great promise in the regenerative medicine landscape, particularly in the treatment of musculoskeletal injury and disease in companion animals.

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Exosome-mediated improvement in membrane integrity and muscle function in dystrophic mice

Cited by 21 publications

References 58 publications

Tailored Extracellular Vesicles: Novel Tool for Tissue Regeneration

Tailored Extracellular Vesicles: Novel Tool for Tissue Regeneration

Therapeutic Application of Extracellular Vesicles-Capsulated Adeno-Associated Virus Vector via nSMase2/Smpd3, Satellite, and Immune Cells in Duchenne Muscular Dystrophy

Regenerative medicine 2.0: extracellular vesicle–based therapeutics for musculoskeletal tissue regeneration

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