Regeneration versus fibrosis in skeletal muscle

Moyer, Adam L.; Wagner, Kathryn R.

doi:10.1097/bor.0b013e32834bac92

Cited by 82 publications

(89 citation statements)

References 28 publications

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“…Following injury, fibroblasts are activated to proliferate, express a-SMA and synthesize ECM molecules (Moyer and Wagner, 2011). In skeletal muscle, this process is initially beneficial in repair of an acute injury during which fibrosis formation may allow injured myofiber stumps to come together as a contractile unit.…”

Section: Discussionmentioning

confidence: 99%

“…In these disorders, myofibers undergo successive rounds of degeneration and regeneration and are gradually replaced by deposition of extracellular matrix (ECM) components produced by fibroblasts. Excessive accumulation of ECM causes isolation of the myofiber from capillaries and other myocytes resulting in reduced contractility and regeneration (Moyer and Wagner, 2011). In acute muscle injury, fibroblasts are activated to proliferate and produce ECM, and subsequently undergo apoptosis upon resolution of the injury (Hinz et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Inhibiting myostatin reverses muscle fibrosis through apoptosis

Zhang

Wagner

2012

Journal of Cell Science

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SummarySkeletal muscle fibrosis is a defining feature of the muscular dystrophies in which contractile myofibers are replaced by fibroblasts, adipocytes and extracellular matrix. This maladaptive response of muscle to repetitive injury is progressive, self-perpetuating and thus far, has been considered irreversible. We have previously shown that myostatin, a known endogenous modulator of muscle growth, stimulates normal muscle fibroblasts to proliferate. Here, we demonstrate that myostatin also regulates the proliferation of dystrophic muscle fibroblasts, and increases resistance of fibroblasts to apoptosis through Smad and MAPK signaling. Inhibition of myostatin signaling pathways with a soluble activin IIB receptor (ActRIIB.Fc) reduces resistance of muscle fibroblasts to apoptosis in vitro. Systemic administration of ActRIIB.Fc in senescent mdx mice, a model of muscular dystrophy, significantly increases the number of muscle fibroblasts undergoing apoptosis. This leads to the reversal of pre-existing muscle fibrosis as determined by histological, biochemical and radiographical criteria. These results demonstrate that skeletal muscle fibrosis can be pharmacologically reversed through induction of fibroblast apoptosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibiting myostatin reverses muscle fibrosis through apoptosis

Zhang

Wagner

2012

Journal of Cell Science

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“…However, fibrosis can progress, leading to incomplete muscle healing. 1 Previous studies have examined the use of drugs, cytokines, cells, and gene therapy attempted to improve muscle recovery. [2][3][4][5][6][7][8][9][10] Recently, we showed that transplantation of human peripheral blood CD133-expressing cells (CD133 + cells) inhibits fibrosis and improves muscle regeneration after skeletal muscle laceration.…”

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confidence: 99%

Magnetic Targeting of Human Peripheral Blood CD133⁺Cells for Skeletal Muscle Regeneration

Ohkawa

Kamei²,

Kamei³

et al. 2013

Tissue Engineering Part C: Methods

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Skeletal muscle injuries often leave lasting functional damage or pain. Muscle injuries are routinely treated conservatively, but the most effective treatment to promote the repair of injured muscles has not yet been established. Our previous report demonstrated that human peripheral blood-derived CD133+ cell transplantation to rat skeletal muscle injury models inhibited fibrosis and enhanced myogenesis after injury. However, the acquisition of a sufficient number of cells remains the limitation for clinical application, as the CD133 + population is rare in human blood. In this study, we applied a magnetic cell targeting system to accumulate transplanted cells in the muscle injury site and to enhance the regenerative effects of CD133 + cell transplantation, focusing on the fact that CD133 + cells are labeled with a magnetic bead for isolation. For the magnetic cell targeting, the magnet field generator was set up to adjust the peak of the magnetic gradient to the injury site of the tibialis anterior muscle, and 1 · 10 4 human peripheral blood CD133 + cells were locally injected into the injury site. This cell number is 10% of that used in the previous study. In another group, the same number of CD133 + cells was injected without magnetic force. The CD133 + cells transplanted with the magnetic force were more accumulated in the muscle injury site compared with the CD133 + cells transplanted without the magnetic force. In addition, the transplantation of CD133+ cells under the magnetic control inhibited fibrous scar formation and promoted angiogenesis and myogenesis, and also upregulated the mRNA expression of myogenic transcription factors, including Pax7, MyoD1 and Myogenin. However, the transplantation of CD133 + cells without the magnetic force failed to demonstrate these effects. Thus, our magnetic cell targeting system enables transplantation of a limited number of CD133 + cells to promote the repair of skeletal muscle injury.

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“…The healing of muscle tissue after an injury comprises a sequence of different steps, which lead to the restoration of the tissue architecture and function 4 . The first step is the inflammatory phase, which is characterized by the formation of a hematoma and an inflammatory cell reaction.…”

Section: Introductionmentioning

confidence: 99%