Bone Marrow Stromal Cell-Derived Exosomes Promote Muscle Healing Following Contusion Through Macrophage Polarization

Luo, Zhiwen; Lin, Jinrong; Sun, Yaying; Chen, Jiwu; Chen, Jiwu

doi:10.1089/scd.2020.0167

Cited by 49 publications

(61 citation statements)

References 47 publications

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“…The extraction procedure for C2C12-Exos was based on a previous method[ 27 ]. 50 mL conditioned culture medium containing 5 mL exosome-free FBS (Exosome-depleted FBS, Gibco), and 0.5 mL of penicillin/streptomycin solution were used to culture C2C12s for 48 h. After the C2C12s had grown to more than 90% confluence, the cells were treated with LPS for 1 d. Then, fresh culture medium was added, and the cells were kept quiescent for 24 h, and then all the supernatant was collected.…”

Section: Methodsmentioning

confidence: 99%

Exosomes derived from inflammatory myoblasts promote M1 polarization and break the balance of myoblast proliferation/differentiation

Luo¹,

Sun²,

Lin³

et al. 2021

WJSC

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BACKGROUND Acute muscle injuries are one of the most common injuries in sports. Severely injured muscles are prone to re-injury due to fibrotic scar formation caused by prolonged inflammation. How to regulate inflammation and suppress fibrosis is the focus of promoting muscle healing. Recent studies have found that myoblasts and macrophages play important roles in the inflammatory phase following muscle injury; however, the crosstalk between these two types of cells in the inflammatory environment, particularly the exosome-related mechanisms, had not been well studied. AIM To evaluate the effects of exosomes from inflammatory C2C12 myoblasts (IF-C2C12-Exos) on macrophage polarization and myoblast proliferation/differentiation. METHODS A model of inflammation was established in vitro by lipopolysaccharide stimulation of myoblasts. C2C12-Exos were isolated and purified from the supernatant of myoblasts by gradient centrifugation. Multiple methods were used to identify the exosomes. Gradient concentrations of IF-C2C12-Exos were added to normal macrophages and myoblasts. PKH67 fluorescence tracing was used to identify the interaction between exosomes and cells. Microscopic morphology, Giemsa stain, and immunofluorescence were carried out for histological analysis. Additionally, ELISA assays, flow cytometry, and western blot were conducted to analyze molecular changes. Moreover, myogenic proliferation was assessed by the BrdU test, scratch assay, and CCK-8 assay. RESULTS We found that the PKH-67-marked C2C12-Exos can be endocytosed by both macrophages and myoblasts. IF-C2C12-Exos induced M1 macrophage polarization and suppressed the M2 phenotype in vitro . In addition, these exosomes also stimulated the inflammatory reactions of macrophages. Furthermore, we demonstrated that IF-C2C12-Exos disrupted the balance of myoblast proliferation/differentiation, leading to enhanced proliferation and suppressed fibrogenic/myogenic differentiation. CONCLUSION IF-C2C12-Exos can induce M1 polarization, resulting in a sustained and aggravated inflammatory environment that impairs myoblast differentiation, and leads to enhanced myogenic proliferation. These results demonstrate why prolonged inflammation occurs after acute muscle injury and provide a new target for the regulation of muscle regeneration.

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Section: Methodsmentioning

confidence: 99%

Exosomes derived from inflammatory myoblasts promote M1 polarization and break the balance of myoblast proliferation/differentiation

Luo¹,

Sun²,

Lin³

et al. 2021

WJSC

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“…Treatment stimulated the formation of new fibers and modulated the expression of genes involved in inflammation, fibrosis, and myogenesis mechanisms ( Iyer et al, 2020 ). Furthermore, another study demonstrated that intramuscular injection of exosomes from BM-MSCs after muscle contusion in mice modified the polarization status of macrophages, alleviated the inflammatory reaction, reduced fibrosis size, promoted muscle regeneration, and improved fast-twitch and tetanus strength ( Luo et al, 2020 ).…”

Section: The Therapeutic Potential Of the Mesenchymal Stromal Cell Secretomementioning

confidence: 99%

Mesenchymal Stromal Cells and Their Secretome: New Therapeutic Perspectives for Skeletal Muscle Regeneration

Sandonà

Pietro

Esposito

et al. 2021

Front. Bioeng. Biotechnol.

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Mesenchymal stromal cells (MSCs) are multipotent cells found in different tissues: bone marrow, peripheral blood, adipose tissues, skeletal muscle, perinatal tissues, and dental pulp. MSCs are able to self-renew and to differentiate into multiple lineages, and they have been extensively used for cell therapy mostly owing to their anti-fibrotic and immunoregulatory properties that have been suggested to be at the basis for their regenerative capability. MSCs exert their effects by releasing a variety of biologically active molecules such as growth factors, chemokines, and cytokines, either as soluble proteins or enclosed in extracellular vesicles (EVs). Analyses of MSC-derived secretome and in particular studies on EVs are attracting great attention from a medical point of view due to their ability to mimic all the therapeutic effects produced by the MSCs (i.e., endogenous tissue repair and regulation of the immune system). MSC-EVs could be advantageous compared with the parental cells because of their specific cargo containing mRNAs, miRNAs, and proteins that can be biologically transferred to recipient cells. MSC-EV storage, transfer, and production are easier; and their administration is also safer than MSC therapy. The skeletal muscle is a very adaptive tissue, but its regenerative potential is altered during acute and chronic conditions. Recent works demonstrate that both MSCs and their secretome are able to help myofiber regeneration enhancing myogenesis and, interestingly, can be manipulated as a novel strategy for therapeutic interventions in muscular diseases like muscular dystrophies or atrophy. In particular, MSC-EVs represent promising candidates for cell free-based muscle regeneration. In this review, we aim to give a complete picture of the therapeutic properties and advantages of MSCs and their products (MSC-derived EVs and secreted factors) relevant for skeletal muscle regeneration in main muscular diseases.

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“…7,21 Recent data suggest that the immunomodulatory activity of BMSCs makes them an even more promising therapeutic tool in terms of cell-based therapies in osteoporosis treatment. 22 However, the metabolic imbalance associated with osteoporosis affects the activity of BMSCs. The cells are losing their valuable biological properties, such as proliferative activity and multipotency.…”

Section: Introductionmentioning

confidence: 99%

“… 7 , 21 Recent data suggest that the immunomodulatory activity of BMSCs makes them an even more promising therapeutic tool in terms of cell‐based therapies in osteoporosis treatment. 22 …”

Section: Introductionmentioning

confidence: 99%

“…Moreover, various miRNA and lncRNA have been shown recently to be involved in the mediation of balance between cell populations of osteoblast‐like or osteoclast‐like nature 7,21 . Recent data suggest that the immunomodulatory activity of BMSCs makes them an even more promising therapeutic tool in terms of cell‐based therapies in osteoporosis treatment 22 …”

Section: Introductionmentioning

confidence: 99%

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Bone marrow stromal cells (BMSCs CD45^‐/CD44⁺/CD73⁺/CD90⁺) isolated from osteoporotic mice SAM/P6 as a novel model for osteoporosis investigation

Sikora

Śmieszek

Marycz

2021

J Cellular Molecular Medi

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Bone Marrow Stromal Cell-Derived Exosomes Promote Muscle Healing Following Contusion Through Macrophage Polarization

Cited by 49 publications

References 47 publications

Exosomes derived from inflammatory myoblasts promote M1 polarization and break the balance of myoblast proliferation/differentiation

Exosomes derived from inflammatory myoblasts promote M1 polarization and break the balance of myoblast proliferation/differentiation

Mesenchymal Stromal Cells and Their Secretome: New Therapeutic Perspectives for Skeletal Muscle Regeneration

Bone marrow stromal cells (BMSCs CD45^‐/CD44⁺/CD73⁺/CD90⁺) isolated from osteoporotic mice SAM/P6 as a novel model for osteoporosis investigation

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Bone Marrow Stromal Cell-Derived Exosomes Promote Muscle Healing Following Contusion Through Macrophage Polarization

Cited by 49 publications

References 47 publications

Exosomes derived from inflammatory myoblasts promote M1 polarization and break the balance of myoblast proliferation/differentiation

Exosomes derived from inflammatory myoblasts promote M1 polarization and break the balance of myoblast proliferation/differentiation

Mesenchymal Stromal Cells and Their Secretome: New Therapeutic Perspectives for Skeletal Muscle Regeneration

Bone marrow stromal cells (BMSCs CD45‐/CD44+/CD73+/CD90+) isolated from osteoporotic mice SAM/P6 as a novel model for osteoporosis investigation

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Bone marrow stromal cells (BMSCs CD45^‐/CD44⁺/CD73⁺/CD90⁺) isolated from osteoporotic mice SAM/P6 as a novel model for osteoporosis investigation