Macrophage Plasticity and the Role of Inflammation in Skeletal Muscle Repair

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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Macrophage Plasticity in Skeletal Muscle Repair

BioMed Research International ◽

10.1155/2014/560629 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 83

Author(s):

Elena Rigamonti ◽

Paola Zordan ◽

Clara Sciorati ◽

Patrizia Rovere-Querini ◽

Silvia Brunelli

Keyword(s):

Skeletal Muscle ◽

Macrophage Polarization ◽

Acute Injury ◽

Environmental Cues ◽

Ongoing Debate ◽

M1 Macrophages ◽

Tissue Healing ◽

Macrophage Plasticity ◽

Macrophage Populations ◽

Available Information

Macrophages are one of the first barriers of host defence against pathogens. Beyond their role in innate immunity, macrophages play increasingly defined roles in orchestrating the healing of various injured tissues. Perturbations of macrophage function and/or activation may result in impaired regeneration and fibrosis deposition as described in several chronic pathological diseases. Heterogeneity and plasticity have been demonstrated to be hallmarks of macrophages. In response to environmental cues they display a proinflammatory (M1) or an alternative anti-inflammatory (M2) phenotype. A lot of evidence demonstrated that after acute injury M1 macrophages infiltrate early to promote the clearance of necrotic debris, whereas M2 macrophages appear later to sustain tissue healing. Whether the sequential presence of two different macrophage populations results from a dynamic shift in macrophage polarization or from the recruitment of new circulating monocytes is a subject of ongoing debate. In this paper, we discuss the current available information about the role that different phenotypes of macrophages plays after injury and during the remodelling phase in different tissue types, with particular attention to the skeletal muscle.

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

Cell Engineering and Regeneration ◽

10.1007/978-3-319-37076-7_2-1 ◽

2018 ◽

pp. 1-30

Author(s):

Johanna Pruller ◽

Peter S. Zammit

Keyword(s):

Skeletal Muscle ◽

Cell Types ◽

Muscle Repair

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The Role of Metabolic Remodeling in Macrophage Polarization and Its Effect on Skeletal Muscle Regeneration

Antioxidants and Redox Signaling ◽

10.1089/ars.2017.7420 ◽

2019 ◽

Vol 30 (12) ◽

pp. 1553-1598 ◽

Cited By ~ 10

Author(s):

Francesca De Santa ◽

Laura Vitiello ◽

Alessio Torcinaro ◽

Elisabetta Ferraro

Keyword(s):

Skeletal Muscle ◽

Muscle Regeneration ◽

Macrophage Polarization ◽

Skeletal Muscle Regeneration ◽

Metabolic Remodeling

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The Role of Inflammation in Traumatic Brain Injury

Neurotrauma ◽

10.1093/med/9780190279431.003.0019 ◽

2018 ◽

pp. 211-232

Author(s):

Sarah C. Hellewell ◽

Bridgette D. Semple ◽

Jenna M. Ziebell ◽

Nicole Bye ◽

Cristina Morganti-Kossmann

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Glial Cells ◽

Immune Cell ◽

Brain Trauma ◽

Multiple Roles ◽

Cell Functions ◽

Macrophage Populations

Inflammation occurring following brain trauma represents a significant constituent of complex secondary responses that dictate patients’ outcome. Although a few decades have passed since its discovery, new aspects of this intriguing phenomenon are still being uncovered, ranging from the multiple roles of mediators regulating the inception, progression, and resolution of neuroinflammation, to the development of antiinflammatory therapies. This review provides a summary of the vast research on traumatic brain injury inflammation. The authors describe the fundamental aspects of cytokine and immune cell functions, the orchestrated collaboration of chemokines and leukocytes, the phenotypic distinction of macrophage populations, and the contribution of glial cells. Among the beneficial properties of neuroinflammation, they briefly discuss cytokines’ impact on neurogenesis; the chapter concludes by touching on the implications of antiinflammatory therapies.

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Harnessing Inorganic Nanoparticles to Direct Macrophage Polarization for Skeletal Muscle Regeneration

Nanomaterials ◽

10.3390/nano10101963 ◽

2020 ◽

Vol 10 (10) ◽

pp. 1963

Author(s):

Francesca Corsi ◽

Felicia Carotenuto ◽

Paolo Di Nardo ◽

Laura Teodori

Keyword(s):

Skeletal Muscle ◽

Muscle Regeneration ◽

Macrophage Polarization ◽

Inorganic Nanoparticles ◽

Skeletal Muscle Regeneration ◽

Full Potential ◽

Significant Progress ◽

Synthetic Scaffolds ◽

Macrophage Plasticity ◽

Biomedical Field

Modulation of macrophage plasticity is emerging as a successful strategy in tissue engineering (TE) to control the immune response elicited by the implanted material. Indeed, one major determinant of success in regenerating tissues and organs is to achieve the correct balance between immune pro-inflammatory and pro-resolution players. In recent years, nanoparticle-mediated macrophage polarization towards the pro- or anti-inflammatory subtypes is gaining increasing interest in the biomedical field. In TE, despite significant progress in the use of nanomaterials, the full potential of nanoparticles as effective immunomodulators has not yet been completely realized. This work discusses the contribution that nanotechnology gives to TE applications, helping native or synthetic scaffolds to direct macrophage polarization; here, three bioactive metallic and ceramic nanoparticles (gold, titanium oxide, and cerium oxide nanoparticles) are proposed as potential valuable tools to trigger skeletal muscle regeneration.

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Role of MSC in the Tumor Microenvironment

Cancers ◽

10.3390/cancers12082107 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2107 ◽

Cited By ~ 6

Author(s):

Ralf Hass

Keyword(s):

Tumor Microenvironment ◽

Cancer Cells ◽

Tumor Development ◽

Tumor Stroma ◽

Cell Types ◽

Cellular Interactions ◽

Cell Functions ◽

Metastatic Behavior ◽

Stem Cell Niches

The tumor microenvironment represents a dynamically composed matrix in which tissue-associated cancer cells are embedded together with a variety of further cell types to form a more or less separate organ-like structure. Constantly mutual interactions between cells of the tumor microenvironment promote continuous restructuring and growth in the tumor. A distinct organization of the tumor stroma also facilitates the formation of transient cancer stem cell niches, thereby contributing to progressive and dynamic tumor development. An important but heterogeneous mixture of cells that communicates among the cancer cells and the different tumor-associated cell types is represented by mesenchymal stroma-/stem-like cells (MSC). Following recruitment to tumor sites, MSC can change their functionalities, adapt to the tumor’s metabolism, undergo differentiation and synergize with cancer cells. Vice versa, cancer cells can alter therapeutic sensitivities and change metastatic behavior depending on the type and intensity of this MSC crosstalk. Thus, close cellular interactions between MSC and cancer cells can eventually promote cell fusion by forming new cancer hybrid cells. Consequently, newly acquired cancer cell functions or new hybrid cancer populations enlarge the plasticity of the tumor and counteract successful interventional strategies. The present review article highlights some important features of MSC within the tumor stroma.

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Hyaluronan as an Immune Regulator in Human Diseases

Physiological Reviews ◽

10.1152/physrev.00052.2009 ◽

2011 ◽

Vol 91 (1) ◽

pp. 221-264 ◽

Cited By ~ 529

Author(s):

Dianhua Jiang ◽

Jiurong Liang ◽

Paul W. Noble

Keyword(s):

Cell Surface ◽

Tissue Injury ◽

Inflammatory Cells ◽

Cell Types ◽

Surface Proteins ◽

Human Diseases ◽

Inflammatory Genes ◽

Extracellular Matrix Components ◽

Injury And Repair

Accumulation and turnover of extracellular matrix components are the hallmarks of tissue injury. Fragmented hyaluronan stimulates the expression of inflammatory genes by a variety of immune cells at the injury site. Hyaluronan binds to a number of cell surface proteins on various cell types. Hyaluronan fragments signal through both Toll-like receptor (TLR) 4 and TLR2 as well as CD44 to stimulate inflammatory genes in inflammatory cells. Hyaluronan is also present on the cell surface of epithelial cells and provides protection against tissue damage from the environment by interacting with TLR2 and TLR4. Hyaluronan and hyaluronan-binding proteins regulate inflammation, tissue injury, and repair through regulating inflammatory cell recruitment, release of inflammatory cytokines, and cell migration. This review focuses on the role of hyaluronan as an immune regulator in human diseases.

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Deficient macrophage autophagy protects mice from Cerium Oxide nanoparticle-induced lung fibrosis

10.21203/rs.3.rs-41389/v1 ◽

2020 ◽

Author(s):

Balasubramanyam Annangi ◽

Zhuyi Lu ◽

Jonathan Bruniaux ◽

Audrey Ridoux ◽

Vanessa Marques da Silva ◽

...

Keyword(s):

Rare Earth ◽

Lung Fibrosis ◽

Interstitial Fibrosis ◽

Macrophage Polarization ◽

Inflammatory Cells ◽

Type I ◽

Potential Health ◽

Pulmonary Exposure ◽

M2 Phenotype

Abstract BackgroundCerium (Ce) is a rare earth element, rapidly oxidizing to form CeO2, and currently used in numerous commercial applications, especially as nanoparticles (NP). The potential health effects of Ce remain uncertain, but literature indicates the development of rare earth pneumoconiosis accompanied with granuloma formation, interstitial fibrosis and inflammation. The exact underlying mechanisms are yet not completely understood, and we propose that autophagy could be an interesting target to study, particularly in macrophages. Therefore, the objective of our study was to investigate the role of macrophagic autophagy after pulmonary exposure to CeO2 NP in mice. Mice lacking the early autophagy gene Atg5 in their myeloid lineage and their wildtype counterparts were exposed to CeO2 NP by single oropharyngeal administration and sacrificed up to one month after. At that time, lung remodeling was thoroughly characterized (inflammatory cells infiltration, expression of fibrotic markers such as αSMA, TGFβ1, total and type I and III collagen deposition), as well as macrophage infiltration (quantification and M1/M2 phenotype). Results: Such pulmonary exposure to CeO2 NP induces a progressive and dose-dependent lung fibrosis in the bronchiolar and alveolar walls, together with the activation of autophagy. Blockade of macrophagic autophagy protects from alveolar but not bronchiolar fibrosis, via the modulation of macrophage polarization towards M2 phenotype. Conclusion: In conclusion, our findings bring novel insight on the role of macrophagic autophagy in lung fibrogenesis, and add to the current awareness of pulmonary macrophages as potential new therapeutic targets for future anti-fibrotic therapies.

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From Innate to Adaptive Immune Response in Muscular Dystrophies and Skeletal Muscle Regeneration: The Role of Lymphocytes

BioMed Research International ◽

10.1155/2014/438675 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 33

Author(s):

Luca Madaro ◽

Marina Bouché

Keyword(s):

Skeletal Muscle ◽

Immune Response ◽

Immune Cells ◽

Current Knowledge ◽

Adaptive Immune Response ◽

Inflammatory Cells ◽

Skeletal Muscle Regeneration ◽

Current View ◽

Muscle Necrosis

Skeletal muscle is able to restore contractile functionality after injury thanks to its ability to regenerate. Following muscle necrosis, debris is removed by macrophages, and muscle satellite cells (MuSCs), the muscle stem cells, are activated and subsequently proliferate, migrate, and form muscle fibers restoring muscle functionality. In most muscle dystrophies (MDs), MuSCs fail to properly proliferate, differentiate, or replenish the stem cell compartment, leading to fibrotic deposition. However, besides MuSCs, interstitial nonmyogenic cells and inflammatory cells also play a key role in orchestrating muscle repair. A complete understanding of the complexity of these mechanisms should allow the design of interventions to attenuate MDs pathology without disrupting regenerative processes. In this review we will focus on the contribution of immune cells in the onset and progression of MDs, with particular emphasis on Duchenne muscular dystrophy (DMD). We will briefly summarize the current knowledge and recent advances made in our understanding of the involvement of different innate immune cells in MDs and will move on to critically evaluate the possible role of cell populations within the acquired immune response. Revisiting previous observations in the light of recent evidence will likely change our current view of the onset and progression of the disease.

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