Influence of microRNAs and exosomes in muscle health and diseases

Lam, Ngoc Thien; Gartz, Melanie; Thomas, Leah; Haberman, Margaret; Strande, Jennifer L.

doi:10.1007/s10974-019-09555-5

Cited by 13 publications

(21 citation statements)

References 160 publications

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“…62 Exosomes are specifically important for maintaining muscle health via autocrine, paracrine, and endocrine signaling. 31 In addition to carrying various signal molecules including myogenic growth factors related to muscle development (eg, IGFs, HGF, FGF-2, PDGF), exosomes also carry small (~23 base pair) noncoding microRNAs (miRNAs) related to tissue regeneration, such as antiapoptotic and antioxidant miRNAs, some of which enhance myogenesis, promote muscle regeneration, and are required for maintenance of normal myocyte health. 31,45 Given their unique surface proteins, exosomes purportedly have faster uptake after muscle injury than other types of EVs.…”

Section: Discussionmentioning

confidence: 99%

“…31 In addition to carrying various signal molecules including myogenic growth factors related to muscle development (eg, IGFs, HGF, FGF-2, PDGF), exosomes also carry small (~23 base pair) noncoding microRNAs (miRNAs) related to tissue regeneration, such as antiapoptotic and antioxidant miRNAs, some of which enhance myogenesis, promote muscle regeneration, and are required for maintenance of normal myocyte health. 31,45 Given their unique surface proteins, exosomes purportedly have faster uptake after muscle injury than other types of EVs. 7 Recent studies also have indicated that exosomes can contribute to muscle regeneration in vivo after laceration (exosomes from adipose-derived stem cells), 13 toxin injection (exosomes from MSCs), 45 and rotator cuff tear (exosomes from adipose-derived stem cells), 63 but changes in muscle function have not been assessed.…”

Section: Discussionmentioning

confidence: 99%

“…28 A possible explanation for the discrepancy between treatment groups is that there are hundreds of cytokines, miRNAs, and other cargoes that vary depending on the condition and origin of the cells used. 31,60,62,63 Previous studies have examined the cargo exosomes, such as specific miRNAs, proteins, and cytokines, but the outcomes varied by cell type and did not specifically explain the underlying mechanisms of improved contractile function, which is the clinical endpoint in recovery from muscle injury.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the composition of exosomes can vary vastly according to the protocols used and cell type of origin used. 26,31,61 Even with standardized procedures, optimizing exosomes for clinical use still faces significant elucidations.…”

Section: Discussionmentioning

confidence: 99%

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Exosomes Isolated From Platelet-Rich Plasma and Mesenchymal Stem Cells Promote Recovery of Function After Muscle Injury

et al. 2020

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Background: Clinical use of platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) has gained momentum as treatment for muscle injuries. Exosomes, or small cell–derived vesicles, could be helpful if they could deliver the same or better physiological effect without cell transplantation into the muscle. Hypothesis: Local delivery of exosomes derived from PRP (PRP-exos) or MSCs (MSC-exos) to injured muscles hastens recovery of contractile function. Study Design: Controlled laboratory study. Methods: In a rat model, platelets were isolated from blood, and MSCs were isolated from bone marrow and expanded in culture; exosomes from both were isolated through ultracentrifugation. The tibialis anterior muscles were injured in vivo using maximal lengthening contractions. Muscles were injected with PRP-exos or MSC-exos (immediately after injury and 5 and 10 days after injury); controls received an equal volume of saline. Histological and biochemical analysis was performed on tissues for all groups. Results: Injury resulted in a significant loss of maximal isometric torque (66% ± 3%) that gradually recovered over 2 weeks. Both PRP-exos and MSC-exos accelerated recovery, with similar faster recovery of contractile function over the saline-treated group at 5, 10, and 15 days after injury ( P < .001). A significant increase in centrally nucleated fibers was seen with both types of exosome groups by day 15 ( P < .01). Genes involved in skeletal muscle regeneration were modulated by different exosomes. Muscles treated with PRP-exos had increased expression of Myogenin gene ( P < .05), whereas muscles treated with MSC-exos had reduced expression of TGF-β ( P < .05) at 10 days after muscle injury. Conclusion: Exosomes derived from PRP or MSCs can facilitate recovery after a muscle strain injury in a small-animal model likely because of factors that can modulate inflammation, fibrosis, and myogenesis. Clinical Relevance: Given their small size, low immunogenicity, and ease with which they can be obtained, exosomes could represent a novel therapy for many orthopaedic ailments.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Exosomes Isolated From Platelet-Rich Plasma and Mesenchymal Stem Cells Promote Recovery of Function After Muscle Injury

et al. 2020

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“…As stated above, bioactive molecules such proteins and miRNA are the effectors of the paracrine action produced by MSC (as well as MSC-S and MSC-EV). Some of these biomolecules can induce myogenesis by direct regulation of myogenic differentiation/myoblast proliferation, property that would enhance SMR acting at the regenerative phase ( 113 ). More important, antimicrobial peptides such as LL-37, hepcidin and β defensins inhibit microbial contamination in the injured tissue (therefore the life-threatening fasciitis) ( 114 , 115 ).…”

Section: Mesenchymal Stromal Cells-based Therapiesmentioning

confidence: 99%

Mesenchymal Stromal Cell-Based Therapies as Promising Treatments for Muscle Regeneration After Snakebite Envenoming

et al. 2021

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Snakebite envenoming is a global neglected disease with an incidence of up to 2.7 million new cases every year. Although antivenoms are so-far the most effective treatment to reverse the acute systemic effects induced by snakebite envenoming, they have a limited therapeutic potential, being unable to completely neutralize the local venom effects. Local damage, such as dermonecrosis and myonecrosis, can lead to permanent sequelae with physical, social, and psychological implications. The strong inflammatory process induced by snake venoms is associated with poor tissue regeneration, in particular the lack of or reduced skeletal muscle regeneration. Mesenchymal stromal cells (MSCs)-based therapies have shown both anti-inflammatory and pro-regenerative properties. We postulate that using allogeneic MSCs or their cell-free products can induce skeletal muscle regeneration in snakebite victims, improving all the three steps of the skeletal muscle regeneration process, mainly by anti-inflammatory activity, paracrine effects, neovascularization induction, and inhibition of tissue damage, instrumental for microenvironment remodeling and regeneration. Since snakebite envenoming occurs mainly in areas with poor healthcare, we enlist the principles and potential of MSCs-based therapies and discuss regulatory issues, good manufacturing practices, transportation, storage, and related-procedures that could allow the administration of these therapies, looking forward to a safe and cost-effective treatment for a so far unsolved and neglected health problem.

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Extracellular vesicles derived from tumour cells as a trigger of energy crisis in the skeletal muscle

Beltrà

Garcia‐Castillo

et al. 2021

J cachexia sarcopenia muscle

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Background Cachexia, a syndrome frequently occurring in cancer patients, is characterized by muscle wasting, altered energy and protein metabolism and impaired myogenesis. Tumour‐derived microvesicles (TMVs) containing proteins, messenger RNAs (mRNAs), and non‐coding RNAs could contribute to cancer‐induced muscle wasting. Methods Differential ultracentrifugation was used to isolate TMVs from the conditioned medium of Lewis lung carcinoma and C26 colon carcinoma cell cultures. TMVs were added to the culture medium of C2C12 myoblasts and myotubes for 24–48–72 h, and the effects on protein and energy metabolism were assessed. TMVs were also isolated from the blood of C26‐bearing mice. MicroRNA (miR) profile of TMVs was obtained by RNA‐seq and validated by digital drop PCR. Selected miRs were overexpressed in C2C12 myoblasts to assess the effects on myogenic differentiation. Results Differentiation was delayed in C2C12 myoblasts exposed to TMVs, according to reduced expression of myosin heavy chain (MyHC; about 62% of controls at Day 4) and myogenin (about 68% of controls at Day 4). As for myotubes, TMVs did not affect the expression of MyHC, while revealed able to modulate mitochondria and oxidative metabolism. Indeed, reduced mRNA levels of PGC‐1α (C = 1 ± 0.2, TMV = 0.57 ± 0.06, normalized fold change, P < 0.05) and Cytochrome C (C = 1 ± 0.2, TMV = 0.65 ± 0.04, normalized fold change, P < 0.05), associated with increased BNIP3 expression (C = 1 ± 0.1, TMV = 1.29 ± 0.2, normalized fold change, P < 0.05), were observed, suggesting reduced mitochondrial biogenesis/amount and enhanced mitophagy. These changes were paralleled by decreased oxygen consumption (C = 686.9 ± 44 pmol/min, TMV = 552.25 ± 24 pmol/min, P < 0.01) and increased lactate levels (C = 0.0063 ± 0.00045 nmol/μL, TMV = 0.0094 ± 0.00087 nmol/μL, P < 0.01). A total of 118 miRs were found in MVs derived from the plasma of the C26 hosts; however, only three of them were down‐regulated (RNA‐seq): miR‐181a‐5p (−1.46 fold change), miR‐375‐3p (−2.52 fold change), and miR‐455‐5p (−3.87 fold change). No correlation could be observed among miRs in the MVs obtained from the blood of the C26 host and those released by C26 cells in the culture medium. Overexpression of miR‐148a‐3p and miR‐181a‐5p in C2C12 myoblasts revealed the ability to impinge on the mRNA levels of Myf5, Myog, and MyHC (Myh4 and Myh7). Conclusions These results show that in C2C12 cultures, TMVs are able to affect both differentiation and the mitochondrial system. Such effects could be related to TMV‐contained miRs.

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Influence of microRNAs and exosomes in muscle health and diseases

Cited by 13 publications

References 160 publications

Exosomes Isolated From Platelet-Rich Plasma and Mesenchymal Stem Cells Promote Recovery of Function After Muscle Injury

Exosomes Isolated From Platelet-Rich Plasma and Mesenchymal Stem Cells Promote Recovery of Function After Muscle Injury

Mesenchymal Stromal Cell-Based Therapies as Promising Treatments for Muscle Regeneration After Snakebite Envenoming

Extracellular vesicles derived from tumour cells as a trigger of energy crisis in the skeletal muscle

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