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Restoration versus reconstruction: cellular mechanisms of skin, nerve and muscle regeneration compared.

Coletti D, Teodori L, Lin Z, Beranudin JF, Adamo S - Regen Med Res (2013)

Bottom Line: In order to investigate the existence a leitmotif of tissue regeneration, we compared the cellular aspects of regeneration of skin, nerve and skeletal muscle, three organs characterized by different types of anatomical and functional organization.The choice of either strategy is influenced by the anatomical, physical and chemical features of the cells as well as by the extracellular matrix typical of a given tissue, which points to the existence of differential, evolutionary-based mechanisms for specific tissue regeneration.The shared, ordered sequence of steps that characterize the regeneration processes examined suggests it may be possible to model this extremely important phenomenon to reproduce multicellular organisms.

View Article: PubMed Central - PubMed

Affiliation: UPMC Univ Paris 06, UR4 Ageing, Stress, Inflammation, 75005 Paris, France ; Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Section of Histology & Medical Embryology, 00161 Rome, Italy ; Interuniversity Institute of Myology, Kragujevac, Italy.

ABSTRACT
In tissues characterized by a high turnover or following acute injury, regeneration replaces damaged cells and is involved in adaptation to external cues, leading to homeostasis of many tissues during adult life. An understanding of the mechanics underlying tissue regeneration is highly relevant to regenerative medicine-based interventions. In order to investigate the existence a leitmotif of tissue regeneration, we compared the cellular aspects of regeneration of skin, nerve and skeletal muscle, three organs characterized by different types of anatomical and functional organization. Epidermis is a stratified squamous epithelium that migrates from the edge of the wound on the underlying dermis to rebuild lost tissue. Peripheral neurons are elongated cells whose neurites are organized in bundles, within an endoneurium of connective tissue; they either die upon injury or undergo remodeling and axon regrowth. Skeletal muscle is characterized by elongated syncytial cells, i.e. muscle fibers, that can temporarily survive in broken pieces; satellite cells residing along the fibers form new fibers, which ultimately fuse with the old ones as well as with each other to restore the previous organization. Satellite cell asymmetrical division grants a reservoir of undifferentiated cells, while other stem cell populations of muscle and non-muscle origin participate in muscle renewal. Following damage, all the tissues analyzed here go through three phases: inflammation, regeneration and maturation. Another common feature is the occurrence of cellular de-differentiation and/or differentiation events, including gene transcription, which are typical of embryonic development. Nonetheless, various strategies are used by different tissues to replace their lost parts. The epidermis regenerates ex novo, whereas neurons restore their missing parts; muscle fibers use a mixed strategy, based on the regrowth of missing parts through reconstruction by means of newborn fibers. The choice of either strategy is influenced by the anatomical, physical and chemical features of the cells as well as by the extracellular matrix typical of a given tissue, which points to the existence of differential, evolutionary-based mechanisms for specific tissue regeneration. The shared, ordered sequence of steps that characterize the regeneration processes examined suggests it may be possible to model this extremely important phenomenon to reproduce multicellular organisms.

No MeSH data available.


Related in: MedlinePlus

Examples of focal injuries. (LEFT) Hematoxilin-and eosin-stained murine skeletal muscle, longitudinally sectioned to show the gaps in three adjacent fibers. The injury likely occurred following an intense exercise session (wheel running). Upon leakage of the broken sarcolemma, factors such as Wnt are released before a fast repair process known as patch repair occurs. In turn, Wnt factors trigger the activation of satellite cells and other resident interstitial cells with myogenic potential, which proliferate, migrate and fuse into small myotubes that ultimately fuse with the damaged fibers. (RIGHT) Toluidine blue-stained semithin section of a murine carotid showing damage, likely due to smooth muscle cell-restricted inactivation of the serum response factor gene. A rupture of the endothelial layer, as well as of the elastin matrix, with exposure of underlying cells is visible; release of intracellular factors (von Willebrand Factor) and exposure of undisclosed antigens (collagen) are essential for the subsequent phases of clot formation, remodeling and repair of the wall defect. Bar = 25 micron.
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Fig1: Examples of focal injuries. (LEFT) Hematoxilin-and eosin-stained murine skeletal muscle, longitudinally sectioned to show the gaps in three adjacent fibers. The injury likely occurred following an intense exercise session (wheel running). Upon leakage of the broken sarcolemma, factors such as Wnt are released before a fast repair process known as patch repair occurs. In turn, Wnt factors trigger the activation of satellite cells and other resident interstitial cells with myogenic potential, which proliferate, migrate and fuse into small myotubes that ultimately fuse with the damaged fibers. (RIGHT) Toluidine blue-stained semithin section of a murine carotid showing damage, likely due to smooth muscle cell-restricted inactivation of the serum response factor gene. A rupture of the endothelial layer, as well as of the elastin matrix, with exposure of underlying cells is visible; release of intracellular factors (von Willebrand Factor) and exposure of undisclosed antigens (collagen) are essential for the subsequent phases of clot formation, remodeling and repair of the wall defect. Bar = 25 micron.

Mentions: As an exhaustive monograph on skeletal muscle regeneration has recently been published [66], we will focus on certain unique features of skeletal muscle fibers that are particularly relevant to regeneration, such as their large size, elongated shape and syncytial nature. Since myofibers can be several millimeters in length, muscle injury and consequent skeletal muscle fiber necrosis are usually segmental (Figure 1, Table 3). Regeneration must be distinguished from various types of muscle fiber repair following different forms of muscle fiber damage that do not induce necrosis, with one example of the latter being patch repair, which restores sarcolemmal integrity by membrane resealing [67, 68]. Even when fiber necrosis (cell death) does occur, the overall extracellular matrix architecture and chemical composition are often preserved (Figure 2). However, while the basement membrane persists as a scaffold, molecules such as collagen IV start disappearing from as early as day 1 [69]. The degradation of these ECM components may be chemotactic in a wide range of cells, including myoblasts. Proteolysis by metalloproteinases mainly contributes to the modulation of the cell surface and the extracellular matrix [70, 71]. Cell surface-associated heparan sulphate proteoglycans, such as syndecans, play a major role in myogenesis in vivo: they are abundant on the surface of myofibers and myogenic cells, and they bind to growth factors relevant to myogenesis.Figure 1


Restoration versus reconstruction: cellular mechanisms of skin, nerve and muscle regeneration compared.

Coletti D, Teodori L, Lin Z, Beranudin JF, Adamo S - Regen Med Res (2013)

Examples of focal injuries. (LEFT) Hematoxilin-and eosin-stained murine skeletal muscle, longitudinally sectioned to show the gaps in three adjacent fibers. The injury likely occurred following an intense exercise session (wheel running). Upon leakage of the broken sarcolemma, factors such as Wnt are released before a fast repair process known as patch repair occurs. In turn, Wnt factors trigger the activation of satellite cells and other resident interstitial cells with myogenic potential, which proliferate, migrate and fuse into small myotubes that ultimately fuse with the damaged fibers. (RIGHT) Toluidine blue-stained semithin section of a murine carotid showing damage, likely due to smooth muscle cell-restricted inactivation of the serum response factor gene. A rupture of the endothelial layer, as well as of the elastin matrix, with exposure of underlying cells is visible; release of intracellular factors (von Willebrand Factor) and exposure of undisclosed antigens (collagen) are essential for the subsequent phases of clot formation, remodeling and repair of the wall defect. Bar = 25 micron.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4375925&req=5

Fig1: Examples of focal injuries. (LEFT) Hematoxilin-and eosin-stained murine skeletal muscle, longitudinally sectioned to show the gaps in three adjacent fibers. The injury likely occurred following an intense exercise session (wheel running). Upon leakage of the broken sarcolemma, factors such as Wnt are released before a fast repair process known as patch repair occurs. In turn, Wnt factors trigger the activation of satellite cells and other resident interstitial cells with myogenic potential, which proliferate, migrate and fuse into small myotubes that ultimately fuse with the damaged fibers. (RIGHT) Toluidine blue-stained semithin section of a murine carotid showing damage, likely due to smooth muscle cell-restricted inactivation of the serum response factor gene. A rupture of the endothelial layer, as well as of the elastin matrix, with exposure of underlying cells is visible; release of intracellular factors (von Willebrand Factor) and exposure of undisclosed antigens (collagen) are essential for the subsequent phases of clot formation, remodeling and repair of the wall defect. Bar = 25 micron.
Mentions: As an exhaustive monograph on skeletal muscle regeneration has recently been published [66], we will focus on certain unique features of skeletal muscle fibers that are particularly relevant to regeneration, such as their large size, elongated shape and syncytial nature. Since myofibers can be several millimeters in length, muscle injury and consequent skeletal muscle fiber necrosis are usually segmental (Figure 1, Table 3). Regeneration must be distinguished from various types of muscle fiber repair following different forms of muscle fiber damage that do not induce necrosis, with one example of the latter being patch repair, which restores sarcolemmal integrity by membrane resealing [67, 68]. Even when fiber necrosis (cell death) does occur, the overall extracellular matrix architecture and chemical composition are often preserved (Figure 2). However, while the basement membrane persists as a scaffold, molecules such as collagen IV start disappearing from as early as day 1 [69]. The degradation of these ECM components may be chemotactic in a wide range of cells, including myoblasts. Proteolysis by metalloproteinases mainly contributes to the modulation of the cell surface and the extracellular matrix [70, 71]. Cell surface-associated heparan sulphate proteoglycans, such as syndecans, play a major role in myogenesis in vivo: they are abundant on the surface of myofibers and myogenic cells, and they bind to growth factors relevant to myogenesis.Figure 1

Bottom Line: In order to investigate the existence a leitmotif of tissue regeneration, we compared the cellular aspects of regeneration of skin, nerve and skeletal muscle, three organs characterized by different types of anatomical and functional organization.The choice of either strategy is influenced by the anatomical, physical and chemical features of the cells as well as by the extracellular matrix typical of a given tissue, which points to the existence of differential, evolutionary-based mechanisms for specific tissue regeneration.The shared, ordered sequence of steps that characterize the regeneration processes examined suggests it may be possible to model this extremely important phenomenon to reproduce multicellular organisms.

View Article: PubMed Central - PubMed

Affiliation: UPMC Univ Paris 06, UR4 Ageing, Stress, Inflammation, 75005 Paris, France ; Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Section of Histology & Medical Embryology, 00161 Rome, Italy ; Interuniversity Institute of Myology, Kragujevac, Italy.

ABSTRACT
In tissues characterized by a high turnover or following acute injury, regeneration replaces damaged cells and is involved in adaptation to external cues, leading to homeostasis of many tissues during adult life. An understanding of the mechanics underlying tissue regeneration is highly relevant to regenerative medicine-based interventions. In order to investigate the existence a leitmotif of tissue regeneration, we compared the cellular aspects of regeneration of skin, nerve and skeletal muscle, three organs characterized by different types of anatomical and functional organization. Epidermis is a stratified squamous epithelium that migrates from the edge of the wound on the underlying dermis to rebuild lost tissue. Peripheral neurons are elongated cells whose neurites are organized in bundles, within an endoneurium of connective tissue; they either die upon injury or undergo remodeling and axon regrowth. Skeletal muscle is characterized by elongated syncytial cells, i.e. muscle fibers, that can temporarily survive in broken pieces; satellite cells residing along the fibers form new fibers, which ultimately fuse with the old ones as well as with each other to restore the previous organization. Satellite cell asymmetrical division grants a reservoir of undifferentiated cells, while other stem cell populations of muscle and non-muscle origin participate in muscle renewal. Following damage, all the tissues analyzed here go through three phases: inflammation, regeneration and maturation. Another common feature is the occurrence of cellular de-differentiation and/or differentiation events, including gene transcription, which are typical of embryonic development. Nonetheless, various strategies are used by different tissues to replace their lost parts. The epidermis regenerates ex novo, whereas neurons restore their missing parts; muscle fibers use a mixed strategy, based on the regrowth of missing parts through reconstruction by means of newborn fibers. The choice of either strategy is influenced by the anatomical, physical and chemical features of the cells as well as by the extracellular matrix typical of a given tissue, which points to the existence of differential, evolutionary-based mechanisms for specific tissue regeneration. The shared, ordered sequence of steps that characterize the regeneration processes examined suggests it may be possible to model this extremely important phenomenon to reproduce multicellular organisms.

No MeSH data available.


Related in: MedlinePlus