Abstract

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.

Highlights

  • Skeletal muscle regeneration (SkMR) is the ability of injured muscles to functionally recover after traumas and is related to the intrinsic healing properties of injured tissue and to the type of injury based on the number of involved myofibers, muscle strength, and loss of contractility [1,2,3]

  • Satellite cells are quiescent in steady-state conditions; after injuries, they proliferate and differentiate to restore skeletal muscle physiology by sequential expression of specific transcription factors, such as Paired box 7 (Pax7) [5,6,7,8], followed by myogenic regulatory factors (MRFs), Myoblast determination protein (MyoD), Myogenic factor 5 (Myf5), Myogenic factor 6 (Myf6), and Myogenin (Myog)

  • The present review provides an update of stem cell and macrophage involvement in SkMR

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Summary

Introduction

Skeletal muscle regeneration (SkMR) is the ability of injured muscles to functionally recover after traumas and is related to the intrinsic healing properties of injured tissue and to the type of injury based on the number of involved myofibers, muscle strength, and loss of contractility [1,2,3]. Satellite cells are quiescent in steady-state conditions; after injuries, they proliferate and differentiate to restore skeletal muscle physiology by sequential expression of specific transcription factors, such as Paired box 7 (Pax7) [5,6,7,8], followed by myogenic regulatory factors (MRFs), Myoblast determination protein (MyoD), Myogenic factor 5 (Myf5), Myogenic factor 6 (Myf6), and Myogenin (Myog). Muscle tissue can be replaced with a mix of white adipocytes and fibrotic cells in a process called fatty degeneration, in which satellite cells can differentiate in both fibrocytes and adipocytes. The present review provides an update of stem cell and macrophage involvement in SkMR

SkMR Biology
Macrophages and Muscle Healing
Macrophages and Myogenic Precursors: A Functional Crosstalk
Cytokines and Muscle Healing
Conclusions and Perspectives
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