Overview of Cell Types Capable of Contributing to Skeletal Muscle Repair and Regeneration

Traumatic injuries, tumor resections, and degenerative diseases can damage skeletal muscle and lead to functional impairment and severe disability. Skeletal muscle regeneration is a complex process that depends on various cell types, signaling molecules, architectural cues, and physicochemical properties to be successful. To promote muscle repair and regeneration, various strategies for skeletal muscle tissue engineering have been developed in the last decades. However, there is still a high demand for the development of new methods and materials that promote skeletal muscle repair and functional regeneration to bring approaches closer to therapies in the clinic that structurally and functionally repair muscle. The combination of stem cells, biomaterials, and biomolecules is used to induce skeletal muscle regeneration. In this review, we provide an overview of different cell types used to treat skeletal muscle injury, highlight current strategies in biomaterial-based approaches, the importance of topography for the successful creation of functional striated muscle fibers, and discuss novel methods for muscle regeneration and challenges for their future clinical implementation.

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Macrophage Plasticity and the Role of Inflammation in Skeletal Muscle Repair

Mediators of Inflammation ◽

10.1155/2013/491497 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 166

Author(s):

Yacine Kharraz ◽

Joana Guerra ◽

Christopher J. Mann ◽

Antonio L. Serrano ◽

Pura Muñoz-Cánoves

Keyword(s):

Skeletal Muscle ◽

Macrophage Polarization ◽

Inflammatory Cells ◽

Cell Types ◽

Muscle Repair ◽

Muscle Stem Cell ◽

Cell Functions ◽

Macrophage Plasticity ◽

Macrophage Populations

Effective repair of damaged tissues and organs requires the coordinated action of several cell types, including infiltrating inflammatory cells and resident cells. Recent findings have uncovered a central role for macrophages in the repair of skeletal muscle after acute damage. If damage persists, as in skeletal muscle pathologies such as Duchenne muscular dystrophy (DMD), macrophage infiltration perpetuates and leads to progressive fibrosis, thus exacerbating disease severity. Here we discuss how dynamic changes in macrophage populations and activation states in the damaged muscle tissue contribute to its efficient regeneration. We describe how ordered changes in macrophage polarization, from M1 to M2 subtypes, can differently affect muscle stem cell (satellite cell) functions. Finally, we also highlight some of the new mechanisms underlying macrophage plasticity and briefly discuss the emerging implications of lymphocytes and other inflammatory cell types in normal versus pathological muscle repair.

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Progressive and Coordinated Mobilization of the Skeletal Muscle Niche throughout Tissue Repair Revealed by Single-Cell Proteomic Analysis

Cells ◽

10.3390/cells10040744 ◽

2021 ◽

Vol 10 (4) ◽

pp. 744

Author(s):

Matthew Borok ◽

Nathalie Didier ◽

Francesca Gattazzo ◽

Teoman Ozturk ◽

Aurelien Corneau ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Stem Cell ◽

Muscle Regeneration ◽

Cell Types ◽

Skeletal Muscle Regeneration ◽

Muscle Repair ◽

Muscle Stem Cell ◽

Muscle Stem Cells ◽

Cell Lineages

Background: Skeletal muscle is one of the only mammalian tissues capable of rapid and efficient regeneration after trauma or in pathological conditions. Skeletal muscle regeneration is driven by the muscle satellite cells, the stem cell population in interaction with their niche. Upon injury, muscle fibers undergo necrosis and muscle stem cells activate, proliferate and fuse to form new myofibers. In addition to myogenic cell populations, interaction with other cell types such as inflammatory cells, mesenchymal (fibroadipogenic progenitors—FAPs, pericytes) and vascular (endothelial) lineages are important for efficient muscle repair. While the role of the distinct populations involved in skeletal muscle regeneration is well characterized, the quantitative changes in the muscle stem cell and niche during the regeneration process remain poorly characterized. Methods: We have used mass cytometry to follow the main muscle cell types (muscle stem cells, vascular, mesenchymal and immune cell lineages) during early activation and over the course of muscle regeneration at D0, D2, D5 and D7 compared with uninjured muscles. Results: Early activation induces a number of rapid changes in the proteome of multiple cell types. Following the induction of damage, we observe a drastic loss of myogenic, vascular and mesenchymal cell lineages while immune cells invade the damaged tissue to clear debris and promote muscle repair. Immune cells constitute up to 80% of the mononuclear cells 5 days post-injury. We show that muscle stem cells are quickly activated in order to form new myofibers and reconstitute the quiescent muscle stem cell pool. In addition, our study provides a quantitative analysis of the various myogenic populations during muscle repair. Conclusions: We have developed a mass cytometry panel to investigate the dynamic nature of muscle regeneration at a single-cell level. Using our panel, we have identified early changes in the proteome of stressed satellite and niche cells. We have also quantified changes in the major cell types of skeletal muscle during regeneration and analyzed myogenic transcription factor expression in satellite cells throughout this process. Our results highlight the progressive dynamic shifts in cell populations and the distinct states of muscle stem cells adopted during skeletal muscle regeneration. Our findings give a deeper understanding of the cellular and molecular aspects of muscle regeneration.

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Stem Cell and Macrophage Roles in Skeletal Muscle Regenerative Medicine

International Journal of Molecular Sciences ◽

10.3390/ijms221910867 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10867

Author(s):

Pasqualina Scala ◽

Laura Rehak ◽

Valentina Giudice ◽

Elena Ciaglia ◽

Annibale Alessandro Puca ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Immune Responses ◽

Muscle Tissue ◽

Peripheral Blood ◽

Cell Types ◽

Innate Immune ◽

Muscle Repair ◽

Innate Immune Responses ◽

Peripheral Cell

In severe muscle injury, skeletal muscle tissue structure and functionality can be repaired through the involvement of several cell types, such as muscle stem cells, and innate immune responses. However, the exact mechanisms behind muscle tissue regeneration, homeostasis, and plasticity are still under investigation, and the discovery of pathways and cell types involved in muscle repair can open the way for novel therapeutic approaches, such as cell-based therapies involving stem cells and peripheral blood mononucleate cells. Indeed, peripheral cell infusions are a new therapy for muscle healing, likely because autologous peripheral blood infusion at the site of injury might enhance innate immune responses, especially those driven by macrophages. In this review, we summarize current knowledge on functions of stem cells and macrophages in skeletal muscle repairs and their roles as components of a promising cell-based therapies for muscle repair and regeneration.

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Overview of Cell Types Capable of Contributing to Skeletal Muscle Repair and Regeneration

Cell Engineering and Regeneration ◽

10.1007/978-3-319-08831-0_2 ◽

2020 ◽

pp. 3-32

Author(s):

Johanna Pruller ◽

Peter S. Zammit

Keyword(s):

Skeletal Muscle ◽

Cell Types ◽

Muscle Repair

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244-OR: Single Nuclei Chromatin and Transcriptome Profiling across Human and Rat Skeletal Muscle Identifies Regulatory Elements, Genes, and Cell Types Associated with Diabetes GWAS Signals

Diabetes ◽

10.2337/db20-244-or ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 244-OR

Author(s):

STEPHEN PARKER ◽

Keyword(s):

Skeletal Muscle ◽

Transcriptome Profiling ◽

Cell Types ◽

Regulatory Elements ◽

Rat Skeletal Muscle

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Annexins and Membrane Repair Dysfunctions in Muscular Dystrophies

International Journal of Molecular Sciences ◽

10.3390/ijms22105276 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5276

Author(s):

Coralie Croissant ◽

Romain Carmeille ◽

Charlotte Brévart ◽

Anthony Bouter

Keyword(s):

Skeletal Muscle ◽

Muscular Dystrophy ◽

Genetic Disorders ◽

Muscle Cells ◽

Cell Types ◽

Clinical Severity ◽

Skeletal Muscle Cells ◽

Muscular Dystrophies ◽

Membrane Repair ◽

Human Skeletal Muscle Cells

Muscular dystrophies constitute a group of genetic disorders that cause weakness and progressive loss of skeletal muscle mass. Among them, Miyoshi muscular dystrophy 1 (MMD1), limb girdle muscular dystrophy type R2 (LGMDR2/2B), and LGMDR12 (2L) are characterized by mutation in gene encoding key membrane-repair protein, which leads to severe dysfunctions in sarcolemma repair. Cell membrane disruption is a physiological event induced by mechanical stress, such as muscle contraction and stretching. Like many eukaryotic cells, muscle fibers possess a protein machinery ensuring fast resealing of damaged plasma membrane. Members of the annexins A (ANXA) family belong to this protein machinery. ANXA are small soluble proteins, twelve in number in humans, which share the property of binding to membranes exposing negatively-charged phospholipids in the presence of calcium (Ca2+). Many ANXA have been reported to participate in membrane repair of varied cell types and species, including human skeletal muscle cells in which they may play a collective role in protection and repair of the sarcolemma. Here, we discuss the participation of ANXA in membrane repair of healthy skeletal muscle cells and how dysregulation of ANXA expression may impact the clinical severity of muscular dystrophies.

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