Key points
Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia.
The extent of cross‐talk between fibroblasts, ...as the source of matrix protein, and satellite cells in humans is unknown. We studied this in human muscle biopsies and cell‐culture studies.
We observed a strong stimulation of myogenesis by human fibroblasts in cell culture.
In biopsies collected 30 days after a muscle injury protocol, fibroblast number increased to four times control levels, where fibroblasts were found to be preferentially located immediately surrounding regenerating muscle fibres.
These novel findings indicate an important role for fibroblasts in supporting the regeneration of muscle fibres, potentially through direct stimulation of satellite cell differentiation and fusion, and contribute to understanding of cell–cell cross‐talk during physiological and pathological muscle remodelling.
Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia. In addition to the indispensable role satellite cells play in muscle regeneration, there is emerging evidence in rodents for a regulatory influence on fibroblast activity. However, the influence of fibroblasts on satellite cells and muscle regeneration in humans is unknown. The purpose of this study was to investigate this in vitro and during in vivo regeneration in humans. Following a muscle injury protocol in young healthy men (n = 7), the number of fibroblasts (TCF7L2+), satellite cells (Pax7+), differentiating myogenic cells (myogenin+) and regenerating fibres (neonatal/embryonic myosin+) was determined from biopsy cross‐sections. Fibroblasts and myogenic precursor cells (MPCs) were also isolated from human skeletal muscle (n = 4) and co‐cultured using different cell ratios, with the two cell populations either in direct contact with each other or separated by a permeable membrane. MPC proliferation, differentiation and fusion were assessed from cells stained for BrdU, desmin and myogenin. On biopsy cross‐sections, fibroblast number was seen to increase, along with myogenic cell number, by d7 and increase further by d30, where fibroblasts were observed to be preferentially located immediately surrounding regenerating muscle fibres. In vitro, the presence of fibroblasts in direct contact with MPCs was found to moderately stimulate MPC proliferation and strongly stimulate both MPC differentiation and MPC fusion. It thus appears, in humans, that fibroblasts exert a strong positive regulatory influence on MPC activity, in line with observations during in vivo skeletal muscle regeneration.
Key points
Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia.
The extent of cross‐talk between fibroblasts, as the source of matrix protein, and satellite cells in humans is unknown. We studied this in human muscle biopsies and cell‐culture studies.
We observed a strong stimulation of myogenesis by human fibroblasts in cell culture.
In biopsies collected 30 days after a muscle injury protocol, fibroblast number increased to four times control levels, where fibroblasts were found to be preferentially located immediately surrounding regenerating muscle fibres.
These novel findings indicate an important role for fibroblasts in supporting the regeneration of muscle fibres, potentially through direct stimulation of satellite cell differentiation and fusion, and contribute to understanding of cell–cell cross‐talk during physiological and pathological muscle remodelling.
The Image as a Living Atlas in the World. An Introduction to George Didi-Huberman’s Image Theory Project and Curatorial PracticeThis article delivers both an overview of the ongoing work of art ...historian Georges Didi-Huberman (b. 1953) and an attempt at analyzing the incarnational conception of images that runs through Didi-Huberman’s image theory. In the Christian tradition, images are the result of an incarnational double-economy. Didi-Huberman’s early interpretations in Fra Angelico, dissemblance et figuration are central to our understanding of this incarnational economy. The visible is capable of entering our flesh; to control this incarnational invasion, Christian tradition has developed a reflexive capacity to read these invasions as images in acts of exegesis. This reflexive exegetical economy is pivotal for Didi-Huberman’s political position regarding our modern use and abuse of images. Confronted with Pier Paolo Pasolini’s conviction that we live in a fascistic state of emergency that blinds our senses with total illumination, Didi-Huberman insists in believing that the described reflexive double-economy is still enabling us to let the visible enter our bodies and light up the darkness of our flesh from within as images – thereby developing our imagination and freeing us from the deadening total image that is fascism.
The myotendinous junction (MTJ), a specialized interface for force transmission between muscle and tendon, has a unique transcriptional activity and is highly susceptible to muscle strain injury. ...Eccentric exercise training is known to reduce this risk of injury, but knowledge of the influence of exercise on the MTJ at the molecular and cellular levels is limited. In this study, 30 subjects were randomized to a single bout of eccentric exercise 1 week prior to tissue sampling (exercised) or no exercise (control). Samples were collected from the semitendinosus as part of reconstruction of the anterior cruciate ligament and divided into fractions containing muscle, MTJ and tendon, respectively. The concentrations of macrophages and satellite cells were counted, and the expression of genes previously known to be active at the MTJ were analyzed by real-time–quantitative PCR. An effect of the single bout of exercise was found on the expression of nestin (NES) and osteocrin (OSTN) mRNA in the MTJ and tendon fractions. Genes earlier identified at the MTJ (COL22A1, POSTN, ADAMTS8, MNS1, NCAM1) were confirmed to be expressed at a significantly higher level in the MTJ compared to muscle and tendon but were unaffected by exercise. In the exercise group a higher concentration of macrophages, but not of satellite cells, was seen in muscle close to the MTJ. The expression of NES and OSTN was higher in human semitendinosus MTJ 1 week after a single session of heavy eccentric exercise. Based on these results, NES and OSTN could have a part in explaining how the MTJ adapts to eccentric exercise.
Macrophages (MPs) exert either beneficial or deleterious effects on tissue repair, depending on their activation/polarization state. They are crucial for adult skeletal muscle repair, notably by ...acting on myogenic precursor cells. However, these interactions have not been fully characterized. Here, we explored both in vitro and in vivo, in human, the interactions of differentially activated MPs with myogenic precursor cells (MPCs) during adult myogenesis and skeletal muscle regeneration. We showed in vitro that through the differential secretion of cytokines and growth factors, proinflammatory MPs inhibited MPC fusion while anti‐inflammatory MPs strongly promoted MPC differentiation by increasing their commitment into differentiated myocytes and the formation of mature myotubes. Furthermore, the in vivo time course of expression of myogenic and MP markers was studied in regenerating human healthy muscle after damage. We observed that regenerating areas containing proliferating MPCs were preferentially associated with MPs expressing proinflammatory markers. In the same muscle, regenerating areas containing differentiating myogenin‐positive MPCs were preferentially coupled to MPs harboring anti‐inflammatory markers. These data demonstrate for the first time in human that MPs sequentially orchestrate adult myogenesis during regeneration of damaged skeletal muscle. These results support the emerging concept that inflammation, through MP activation, controls stem cell fate and coordinates tissue repair. STEM CELLS2013;31:384–396
The articles main hypothesis is, following Vilém Flusser, that modern imagery in general is 'technical', which means its images are images of concepts. As such they are difficult to distinguish ...phenomenologically and semiotically from their environment and therefore
difficult to identify as images. From this outset the main argument is that certain modern images are capable of revealing this technicality by confronting the viewer with a concrete visibility forcing discursive relocations of the knowledge integral to perceiving them. The article develops
this argument via the understanding of images of Gottfried Boehm and Michel Foucault in connection with analyses of photographs of the Russian artist Alexander Rodchenko and paintings by the Danish painters J. F. Willumsen and Erik Hoppe.
Abstract The articles main hypothesis is, following Vilém Flusser, that modern imagery in general is ‘technical’, which means its images are images of concepts. As such they are difficult to ...distinguish phenomenologically and semiotically from their environment and therefore difficult to identify as images. From this outset the main argument is that certain modern images are capable of revealing this technicality by confronting the viewer with a concrete visibility forcing discursive relocations of the knowledge integral to perceiving them. The article develops this argument via the understanding of images of Gottfried Boehm and Michel Foucault in connection with analyses of photographs of the Russian artist Alexander Rodchenko and paintings by the Danish painters J. F. Willumsen and Erik Hoppe.
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