scholarly journals Muscle progenitor cells are required for the regenerative response and prevention of adipogenesis after limb ischemia

2020 ◽  
Author(s):  
Hasan Abbas ◽  
Lindsey A. Olivere ◽  
Michael E. Padgett ◽  
Cameron A. Schmidt ◽  
Brian F. Gilmore ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Progenitor Cells ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Ischemic Injury ◽  
Limb Ischemia ◽  
Normal Muscle ◽  
Mouse Muscle ◽  
Muscle Progenitor Cells ◽  
Artery Disease

AbstractPeripheral artery disease (PAD) is nearly as common as coronary artery disease, but few effective treatments exist, and it is associated with significant morbidity and mortality. Although PAD studies have focused on the vascular response to ischemia, skeletal muscle cells play a critically important role in determining the phenotypic manifestation of PAD. Here, we demonstrate that genetic ablation of Pax7+ muscle progenitor cells (MPCs, or satellite cells) in a murine model of hind limb ischemia (HLI) resulted in a complete absence of normal muscle regeneration following ischemic injury, despite a lack of morphological or physiological changes in resting muscle. Compared to ischemic muscle of control mice (Pax7WT), the ischemic limb of Pax7-deficient mice (Pax7Δ) was unable to generate significant force 7- or 28-days after HLI in ex vivo force measurement studies. A dramatic increase in adipose infiltration was observed 28 days after HLI in Pax7Δ mice, which replaced functional muscle. To investigate the mechanism of this adipogenic change, mice with inhibition of fibro/adipogenic precursors (FAPs), another pool of MPCs, were subjected to HLI. Inhibition of FAPs decreased muscle adipose fat but increased fibrosis. MPCs cultured from mouse muscle tissue failed to form myotubes in vitro following depletion of satellite cells in vivo, and they displayed an increased propensity to differentiate into fat in adipogenic medium. Importantly, this phenotype was recapitulated in patients with critical limb ischemia (CLI), the most severe form of PAD. Skeletal muscle samples from CLI patients demonstrated an increase in adipose deposition in more ischemic regions of muscle, which corresponded with a decrease in the number of satellite cells in those regions. Collectively, these data demonstrate that Pax7+ MPCs are required for normal muscle regeneration after ischemic injury, and they suggest that targeting muscle regeneration may be an important therapeutic approach to prevent muscle degeneration in PAD.

scholarly journals Syndecan-4-Expressing Muscle Progenitor Cells in the SP Engraft as Satellite Cells during Muscle Regeneration

2009 ◽  
Vol 4 (3) ◽  
pp. 217-225 ◽  
Author(s):  
Kathleen Kelly Tanaka ◽  
John K. Hall ◽  
Andrew A. Troy ◽  
D.D.W. Cornelison ◽  
Susan M. Majka ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Muscle Progenitor Cells

scholarly journals Metformin alleviates muscle wasting post-thermal injury by increasing Pax7-positive muscle progenitor cells

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yusef Yousuf ◽  
Andrea Datu ◽  
Ben Barnes ◽  
Saeid Amini-Nik ◽  
Marc G. Jeschke
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Progenitor Cells ◽  
Satellite Cells ◽  
Muscle Wasting ◽  
Burn Injury ◽  
Metabolic Effects ◽  
Metformin Treatment ◽  
Muscle Catabolism ◽  
Muscle Progenitor Cells

Abstract Background Profound skeletal muscle wasting and weakness is common after severe burn and persists for years after injury contributing to morbidity and mortality of burn patients. Currently, no ideal treatment exists to inhibit muscle catabolism. Metformin is an anti-diabetic agent that manages hyperglycemia but has also been shown to have a beneficial effect on stem cells after injury. We hypothesize that metformin administration will increase protein synthesis in the skeletal muscle by increasing the proliferation of muscle progenitor cells, thus mitigating muscle atrophy post-burn injury. Methods To determine whether metformin can attenuate muscle catabolism following burn injury, we utilized a 30% total burn surface area (TBSA) full-thickness scald burn in mice and compared burn injuries with and without metformin treatment. We examined the gastrocnemius muscle at 7 and 14 days post-burn injury. Results At 7 days, burn injury significantly reduced myofiber cross-sectional area (CSA) compared to sham, p < 0.05. Metformin treatment significantly attenuated muscle catabolism and preserved muscle CSA at the sham size. To investigate metformin’s effect on satellite cells (muscle progenitors), we examined changes in Pax7, a transcription factor regulating the proliferation of muscle progenitors. Burned animals treated with metformin had a significant increase in Pax7 protein level and the number of Pax7-positive cells at 7 days post-burn, p < 0.05. Moreover, through BrdU proliferation assay, we show that metformin treatment increased the proliferation of satellite cells at 7 days post-burn injury, p < 0.05. Conclusion In summary, metformin’s various metabolic effects and its modulation of stem cells make it an attractive alternative to mitigate burn-induced muscle wasting while also managing hyperglycemia.

scholarly journals Trim33 (Tif1γ) is not required for skeletal muscle development or regeneration but suppresses cholecystokinin expression

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Cassie A. Parks ◽  
Katherine Pak ◽  
Iago Pinal-Fernandez ◽  
Wilson Huang ◽  
Assia Derfoul ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Knockout Mice ◽  
Muscle Regeneration ◽  
Skeletal Muscles ◽  
Muscle Development ◽  
Conditional Knockout ◽  
C2c12 Cells ◽  
Mouse Muscle ◽  
Muscle Histology

AbstractThe expression of Trim33 (Tif1γ) increases in skeletal muscles during regeneration and decreases upon maturation. Although Trim33 is required for the normal development of other tissues, its role in skeletal muscle is unknown. The current study aimed to define the role of Trim33 in muscle development and regeneration. We generated mice with muscle-specific conditional knockout of Trim33 by combining floxed Trim33 and Cre recombinase under the Pax7 promoter. Muscle regeneration was induced by injuring mouse muscles with cardiotoxin. We studied the consequences of Trim33 knockdown on viability, body weight, skeletal muscle histology, muscle regeneration, and gene expression. We also studied the effect of Trim33 silencing in satellite cells and the C2C12 mouse muscle cell line. Although Trim33 knockdown mice weighed less than control mice, their skeletal muscles were histologically unremarkable and regenerated normally following injury. Unexpectedly, RNAseq analysis revealed dramatically increased expression of cholecystokinin (CCK) in regenerating muscle from Trim33 knockout mice, satellite cells from Trim33 knockout mice, and C2C12 cells treated with Trim33 siRNA. Trim33 knockdown had no demonstrable effect on muscle differentiation or regeneration. However, Trim33 knockdown induced CCK expression in muscle, suggesting that suppression of CCK expression requires Trim33.

scholarly journals Cellular senescence-mediated exacerbation of Duchenne muscular dystrophy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hidetoshi Sugihara ◽  
Naomi Teramoto ◽  
Katsuyuki Nakamura ◽  
Takanori Shiga ◽  
Taku Shirakawa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Strength ◽  
Progenitor Cells ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Mesenchymal Progenitor Cells

Abstract Duchenne muscular dystrophy (DMD) is a progressive disease characterised by chronic muscle degeneration and inflammation. Our previously established DMD model rats (DMD rats) have a more severe disease phenotype than the broadly used mouse model. We aimed to investigate the role of senescence in DMD using DMD rats and patients. Senescence was induced in satellite cells and mesenchymal progenitor cells, owing to the increased expression of CDKN2A, p16- and p19-encoding gene. Genetic ablation of p16 in DMD rats dramatically restored body weight and muscle strength. Histological analysis showed a reduction of fibrotic and adipose tissues invading skeletal muscle, with increased muscle regeneration. Senolytic drug ABT263 prevented loss of body weight and muscle strength, and increased muscle regeneration in rats even at 8 months—the late stage of DMD. Moreover, senescence markers were highly expressed in the skeletal muscle of DMD patients. In situ hybridization of CDKN2A confirmed the expression of it in satellite cells and mesenchymal progenitor cells in patients with DMD. Collectively, these data provide new insights into the integral role of senescence in DMD progression.

scholarly journals Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Naoki Ito ◽  
Isao Kii ◽  
Noriaki Shimizu ◽  
Hirotoshi Tanaka ◽  
Shin’ichi Takeda
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Progenitor Cells ◽  
Satellite Cells ◽  
Therapeutic Approaches ◽  
Cell Staining ◽  
Cell Sources ◽  
Heterogenous Population ◽  
Calcein Am ◽  
Muscle Progenitor Cells

Abstract Satellite cells comprise a functionally heterogeneous population of stem cells in skeletal muscle. Separation of an undifferentiated subpopulation and elucidation of its molecular background are necessary to identify the reprogramming factors to induce skeletal muscle progenitor cells. In this study, we found that intracellular esterase activity distinguishes a subpopulation of cultured satellite cells with high stemness using esterase-sensitive cell staining reagent, calcein-AM. Gene expression analysis of this subpopulation revealed that defined combinations of transcription factors (Pax3, Mef2b, and Pitx1 or Pax7, Mef2b, and Pitx1 in embryonic fibroblasts, and Pax7, Mef2b and MyoD in adult fibroblasts) reprogrammed fibroblasts into skeletal muscle progenitor cells. These reprogrammed cells formed Dystrophin-positive mature muscle fibers when transplanted into a mouse model of Duchenne muscular dystrophy. These results highlight the new marker for heterogenous population of cultured satellite cells, potential therapeutic approaches and cell sources for degenerative muscle diseases.

scholarly journals Stem Cell Aging in Skeletal Muscle Regeneration and Disease

2020 ◽  
Vol 21 (5) ◽  
pp. 1830 ◽  
Author(s):  
Hiroyuki Yamakawa ◽  
Dai Kusumoto ◽  
Hisayuki Hashimoto ◽  
Shinsuke Yuasa
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Muscle Regeneration ◽  
Muscle Injury ◽  
Skeletal Muscle Regeneration ◽  
Cell Aging ◽  
Regeneration Ability ◽  
Stem Cell Aging ◽  
Muscle Progenitor Cells

Skeletal muscle comprises 30–40% of the weight of a healthy human body and is required for voluntary movements in humans. Mature skeletal muscle is formed by multinuclear cells, which are called myofibers. Formation of myofibers depends on the proliferation, differentiation, and fusion of muscle progenitor cells during development and after injury. Muscle progenitor cells are derived from muscle satellite (stem) cells (MuSCs), which reside on the surface of the myofiber but beneath the basement membrane. MuSCs play a central role in postnatal maintenance, growth, repair, and regeneration of skeletal muscle. In sedentary adult muscle, MuSCs are mitotically quiescent, but are promptly activated in response to muscle injury. Physiological and chronological aging induces MuSC aging, leading to an impaired regenerative capability. Importantly, in pathological situations, repetitive muscle injury induces early impairment of MuSCs due to stem cell aging and leads to early impairment of regeneration ability. In this review, we discuss (1) the role of MuSCs in muscle regeneration, (2) stem cell aging under physiological and pathological conditions, and (3) prospects related to clinical applications of controlling MuSCs.

Sign in / Sign up

Export Citation Format

Share Document