scholarly journals Bioinspired electrospun dECM scaffolds guide cell growth and control the formation of myotubes

2021 ◽  
Vol 7 (20) ◽  
pp. eabg4123
Author(s):  
Mollie M. Smoak ◽  
Katie J. Hogan ◽  
K. Jane Grande-Allen ◽  
Antonios G. Mikos
Keyword(s):  
Skeletal Muscle ◽  
Physicochemical Properties ◽  
High Capacity ◽  
Skeletal Muscle Regeneration ◽  
Functional Deficits ◽  
Myotube Formation ◽  
Acute Injuries ◽  
One Step ◽  
And Control ◽  
Mouse Myoblast

While skeletal muscle has a high capacity for endogenous repair in acute injuries, volumetric muscle loss can leave long-lasting or permanent structural and functional deficits to the injured muscle and surrounding tissues. With clinical treatments failing to repair lost tissue, there is a great need for a tissue-engineered therapy to promote skeletal muscle regeneration. In this study, we aim to assess the potential for electrospun decellularized skeletal muscle extracellular matrix (dECM) with tunable physicochemical properties to control mouse myoblast growth and myotube formation. The material properties as well as cell behavior – growth and differentiation – were assessed in response to modulation of crosslinking and scaffold architecture. The fabrication of a bioactive dECM-based system with tunable physicochemical properties that can control myotube formation has several applications in skeletal muscle engineering and may bring the field one step closer to developing a therapy to address these unmet clinical needs.

scholarly journals Loss of Parkin Results in Altered Muscle Stem Cell Differentiation during Regeneration

2020 ◽  
Vol 21 (21) ◽  
pp. 8007
Author(s):  
Marcos V. Esteca ◽  
Matheus B. Severino ◽  
João G. Silvestre ◽  
Gustavo Palmeira dos Santos ◽  
Letícia Tamborlin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
High Capacity ◽  
Stem Cell Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Post Injury ◽  
Cross Sectional ◽  
Myoblast Cell Line ◽  
Myoblast Cell

The high capacity of the skeletal muscle to regenerate is due to the presence of muscle stem cells (MuSCs, or satellite cells). The E3 ubiquitin ligase Parkin is a key regulator of mitophagy and is recruited to mitochondria during differentiation of mouse myoblast cell line. However, the function of mitophagy during regeneration has not been investigated in vivo. Here, we have utilized Parkin deficient (Parkin–/–) mice to investigate the role of Parkin in skeletal muscle regeneration. We found a persistent deficiency in skeletal muscle regeneration in Parkin–/– mice after cardiotoxin (CTX) injury with increased area of fibrosis and decreased cross-sectional area (CSA) of myofibres post-injury. There was also a significant modulation of MuSCs differentiation and mitophagic markers, with altered mitochondrial proteins during skeletal muscle regeneration in Parkin–/– mice. Our data suggest that Parkin-mediated mitophagy plays a key role in skeletal muscle regeneration and is necessary for MuSCs differentiation.

scholarly journals Simvastatin impairs myoblast proliferation and myotube formation of C2C12 myoblasts and in mouse skeletal muscle

2021 ◽  
Author(s):  
Gerda M Sanvee ◽  
Jamal Bouitbir ◽  
Stephan Kraehenbuehl
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Plasma Membrane Permeability ◽  
Ki 67 ◽  
C2c12 Myoblasts ◽  
Mouse Skeletal Muscle ◽  
Myotube Formation ◽  
Myoblast Proliferation ◽  
Adam 12

Abstract Statins reduce cardiovascular complications in patients with high LDL-cholesterol but are associated with myopathy. We investigated the possibility that statins impair skeletal muscle regeneration by assessing simvastatin toxicity on C2C12 myoblasts and myotubes and mouse skeletal muscle. Simvastatin increased plasma membrane permeability and decreased the cellular ATP content in both myoblasts and myotubes, but with a stronger effect on myoblasts. While insulin prevented cytotoxicity up to 8 hours after addition of simvastatin to myotubes, prevention in myoblasts required simultaneous addition. Mevalonate and geranylgeraniol also prevented simvastatin-associated cytotoxicity on myoblasts and myotubes. Simvastatin impaired the phosphorylation of the insulin receptor (IR β), Akt ser473 and S6rp, and increased phosphorylation of AMPK thr172 in both myotubes and myoblasts, which was prevented by insulin and mevalonate. Simvastatin impaired oxygen consumption and increased superoxide production by myoblasts and myotubes and induced apoptosis via cytochromc c release. In addition, simvastatin impaired proliferation and fusion of myoblasts to myotubes by inhibiting the expression of the nuclear transcription factor MyoD and of the metalloprotease ADAM-12. Decreased expression of the proliferation factor Ki-67 and of ADAM-12 were also observed in gastrocnemius of mice treated with simvastatin. In conclusion, myoblasts were more susceptible to the toxic effects of simvastatin and simvastatin impaired myoblast proliferation and myotube formation. Impaired muscle regeneration represents a new mechanism of statin myotoxicity and may be important in statin-associated myopathy.

scholarly journals The Role of Satellite Cells in Skeletal Muscle Regeneration—The Effect of Exercise and Age

Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1056
Author(s):  
Agnieszka Kaczmarek ◽  
Mateusz Kaczmarek ◽  
Maria Ciałowicz ◽  
Filipe Manuel Clemente ◽  
Paweł Wolański ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Inflammatory Cells ◽  
Skeletal Muscle Regeneration ◽  
Vigorous Exercise ◽  
Fiber Damage ◽  
Current State ◽  
Ability To Regenerate ◽  
And Control

The population of satellite cells (mSCs) is highly diversified. The cells comprising it differ in their ability to regenerate their own population and differentiate, as well as in the properties they exhibit. The heterogeneity of this group of cells is evidenced by multiple differentiating markers that enable their recognition, classification, labeling, and characterization. One of the main tasks of satellite cells is skeletal muscle regeneration. Myofibers are often damaged during vigorous exercise in people who participate in sports activities. The number of satellite cells and the speed of the regeneration processes that depend on them affect the time structure of an athlete’s training. This process depends on inflammatory cells. The multitude of reactions and pathways that occur during the regeneration process results in the participation and control of many factors that are activated and secreted during muscle fiber damage and at different stages of its regeneration. However, not all of them are well understood yet. This paper presents the current state of knowledge on satellite cell-dependent skeletal muscle regeneration. Studies describing the effects of various forms of exercise and age on this process were reviewed.

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