Platelet-Rich Plasma Enhances Equine Skeletal Muscle Regeneration in a Bupivacaine-Induced Muscle Injury Model

Herein, the structural effect of autologous platelet-rich plasma (PRP) on posttraumatic skeletal muscle regeneration in rats with chronic hyperglycemia (CH) was tested. 130 white laboratory male rats divided into four groups (I—control; II—rats with CH; III—rats with CH and PRP treatment; and IV—rats for CH confirmation) were used for the experiment. CH was simulated by streptozotocin and nicotinic acid administration. Triceps surae muscle injury was reproduced by transverse linear incision. Autologous PRP was used in order to correct the possible negative CH effect on skeletal muscle recovery. On the 28th day after the injury, the regenerating muscle fiber and blood vessel number in the CH+PRP group were higher than those in the CH rats. However, the connective tissue area in the CH group was larger than that in the CH+PRP animals. The amount of agranulocytes in the regenerating muscle of the CH rats was lower compared to that of the CH+PRP group. The histological analysis of skeletal muscle recovery in CH+PRP animals revealed more intensive neoangiogenesis compared to that in the CH group. Herewith, the massive connective tissue development and inflammation signs were observed within the skeletal muscle of CH rats. Obtained results suggest that streptozotocin-induced CH has a negative effect on posttraumatic skeletal muscle regeneration, contributing to massive connective tissue development. The autologous PRP injection promotes muscle recovery process in rats with CH, shifting it away from fibrosis toward the complete muscular organ repair.

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Fibroadipogenic Progenitors contribute to microvascular repair during skeletal muscle regeneration

10.1101/2021.09.06.459112 ◽

2021 ◽

Author(s):

David Ollitrault ◽

Valentina Buffa ◽

Rosamaria Correra ◽

Angeliqua Sayed ◽

Benedicte Hoareau ◽

...

Keyword(s):

Skeletal Muscle ◽

Endothelial Cell ◽

Cell Fate ◽

Muscle Regeneration ◽

Muscle Injury ◽

Glucose Deprivation ◽

Muscle Disease ◽

Skeletal Muscle Regeneration ◽

Local Source ◽

Vascular Regeneration

Skeletal muscle injury results in a disruption of the muscle bed vascular network. A local source of vascular progenitors during muscle regeneration has not been clearly identified. Fibroadipogenic progenitors (FAPs) are required for proper regeneration, however they can also directly contribute to fibrotic and fatty infiltration in response to chronic muscle injury and muscle disease. We show here that acute muscle injury leads to hypoxia and glucose deprivation, triggering FAP proliferation and differentiation into endothelial cells in vitro and in vivo. In response to glucose deprivation, FAPs down regulate fibrotic and fat associated genes and acquire an endothelial cell fate, which is dependent upon mTORC2-HIF2a-eNOS pathway. These findings bring new insights into the mechanisms of vascular regeneration during muscle regeneration and define a highly plastic resident progenitor population that responds to oxygen/glucose-deprivation induced cell stress by promoting an endothelial cell fate.

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PL-003 BMSCs transplantation aggravate inflammation, oxidative stress, fibrosis and impair skeletal muscle regeneration

Exercise Biochemistry Review ◽

10.14428/ebr.v1i1.8073 ◽

2018 ◽

Vol 1 (1) ◽

Author(s):

Xiaoguang Liu ◽

Weihua Xiao ◽

Lifang Zhen ◽

Yongzhan Zhou ◽

Jian Shou

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Matrix Metalloproteinases ◽

Inflammatory Cytokines ◽

Muscle Regeneration ◽

Muscle Injury ◽

Treated Group ◽

Skeletal Muscle Regeneration ◽

Skeletal Muscle Contusion ◽

And Oxidative Stress

Objective Skeletal muscle contusion is one of the most common muscle injury in sports medicine and traumatology. Bone marrow mesenchymal stem cells (BMSCs) transplantation is a promising strategy for muscle regeneration. However, the roles of BMSCs, especially the mechanisms involved, in the regeneration of contused skeletal muscle are still not fully recognized. The aim of the study is to evaluate the potential of BMSCs transplantation for muscle regeneration and mechanisms involved after contusion. Methods Ninety-nine C57BL/6J mice were divided into three groups: control group (n=11), muscle contusion and BMSCs treated group (n=44), muscle contusion and sham treated group (n=44). BMSCs were immediately transplanted into gastrocnemius muscles (GMs) following direct contusion. At different time points (3, 6, 12 and 24 days) post-injury, the animals were killed and then GMs were harvested. Morphological and gene expression analyses were used to elevate the effect of BMSCs transplantation and mechanisms involved. Results The results indicate that BMSCs transplantation impairs muscle regeneration, as well as more fibrotic scar formation after skeletal muscle contusion. Furthermore, macrophages, inflammatory cytokines, chemokines, matrix metalloproteinases and oxidative stress related enzymes were significantly increased after BMSCs transplantation. These results suggest that BMSCs transplantation impairs skeletal muscle regeneration and that macrophages, inflammatory cytokines, chemokines, matrix metalloproteinases and oxidative stress related enzymes may be involved in the process. Conclusions BMSCs transplantation aggravates inflammation, oxidative stress and fibrosis, and impairs skeletal muscle regeneration, which shed new light on the role of BMSCs in regenerative medicine and cautions the application of BMSCs for muscle injury.

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Necdin mediates skeletal muscle regeneration by promoting myoblast survival and differentiation

The Journal of Cell Biology ◽

10.1083/jcb.200701027 ◽

2007 ◽

Vol 179 (2) ◽

pp. 305-319 ◽

Cited By ~ 39

Author(s):

Daniela Deponti ◽

Stéphanie François ◽

Silvia Baesso ◽

Clara Sciorati ◽

Anna Innocenzi ◽

...

Keyword(s):

Skeletal Muscle ◽

Transgenic Mice ◽

Satellite Cell ◽

Muscle Regeneration ◽

Muscle Injury ◽

Muscle Fibers ◽

Skeletal Muscle Regeneration ◽

Muscle Degeneration ◽

Wild Type ◽

Cell Type

Regeneration of muscle fibers that are lost during pathological muscle degeneration or after injuries is sustained by the production of new myofibers. An important cell type involved in muscle regeneration is the satellite cell. Necdin is a protein expressed in satellite cell–derived myogenic precursors during perinatal growth. However, its function in myogenesis is not known. We compare transgenic mice that overexpress necdin in skeletal muscle with both wild-type and necdin null mice. After muscle injury the necdin null mice show a considerable defect in muscle healing, whereas mice that overexpress necdin show a substantial increase in myofiber regeneration. We also find that in muscle, necdin increases myogenin expression, accelerates differentiation, and counteracts myoblast apoptosis. Collectively, these data clarify the function and mechanism of necdin in skeletal muscle and show the importance of necdin in muscle regeneration.

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Myoprotective effects of bFGF on skeletal muscle injury in pressure-related deep tissue injury in rats

Burns & Trauma ◽

10.1186/s41038-016-0051-y ◽

2016 ◽

Vol 4 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Hongxue Shi ◽

Haohuang Xie ◽

Yan Zhao ◽

Cai Lin ◽

Feifei Cui ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Regeneration ◽

Muscle Injury ◽

Muscle Development ◽

Tissue Injury ◽

Skeletal Muscle Regeneration ◽

Deep Tissue ◽

External Compression ◽

Deep Tissue Injury ◽

Skeletal Muscle Injury

Abstract Background Pressure ulcers (PUs) are a major clinical problem that constitutes a tremendous economic burden on healthcare systems. Deep tissue injury (DTI) is a unique serious type of pressure ulcer that arises in skeletal muscle tissue. DTI arises in part because skeletal muscle tissues are more susceptible than skin to external compression. Unfortunately, few effective therapies are currently available for muscle injury. Basic fibroblast growth factor (bFGF), a potent mitogen and survival factor for various cells, plays a crucial role in the regulation of muscle development and homeostasis. The main purpose of this study was to test whether local administration of bFGF could accelerate muscle regeneration in a rat DTI model. Methods Male Sprague Dawley (SD) rats (age 12 weeks) were individually housed in plastic cages and a DTI PU model was induced according to methods described before. Animals were randomly divided into three groups: a normal group, a PU group treated with saline, and a PU group treated with bFGF (10 μg/0.1 ml) subcutaneously near the wound. Results We found that application of bFGF accelerated the rate of wound closure and promoted cell proliferation and tissue angiogenesis. In addition, compared to saline administration, bFGF treatment prevented collagen deposition, a measure of fibrosis, and up-regulated the myogenic marker proteins MyHC and myogenin, suggesting bFGF promoted injured muscle regeneration. Moreover, bFGF treatment increased levels of myogenesis-related proteins p-Akt and p-mTOR. Conclusions Our findings show that bFGF accelerated injured skeletal muscle regeneration through activation of the PI3K/Akt/mTOR signaling pathway and suggest that administration of bFGF is a potential therapeutic strategy for the treatment of skeletal muscle injury in PUs.

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Downregulated miR-204 Promotes Skeletal Muscle Regeneration

BioMed Research International ◽

10.1155/2020/3183296 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Ya Tan ◽

Linyuan Shen ◽

Mailin Gan ◽

Yuan Fan ◽

Xiao Cheng ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Regeneration ◽

Muscle Injury ◽

Target Genes ◽

C2c12 Cell ◽

Skeletal Muscle Regeneration ◽

Luciferase Reporter ◽

Limited Information ◽

Reporter System ◽

Skeletal Muscle Injury

Skeletal muscle is the most abundant and a highly plastic tissue of the mammals, especially when it comes to regenerate after trauma, but there is limited information about the mechanism of muscle repair and its regeneration. In the present study, we found that miR-204 is downregulated after skeletal muscle injury. In vitro experiments showed that over-expression of miR-204 by transfecting with miR-204 mimics suppressed C2C12 cell proliferation, migration, and blocked subsequent differentiation, whereas inhibition of miR-204 by transfecting with miR-204 inhibitor showed the converse effects. Furthermore, through the dual luciferase reporter system, we demonstrated that miR-204 can target the 3’UTR regions of Pax7, IGF1, and Mef2c and inhibit their expression. Taken together, our results suggest that Pax7, IGF1, and Mef2c are the target genes of miR-204 in the process of myoblasts proliferation, cell migration, and differentiation, respectively, and may contribute to mouse skeletal muscle regeneration. Our results may provide new ideas and references for the skeletal muscle study and may also provide therapeutic strategies of skeletal muscle injury.

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PDGFRα mediated survival of myofibroblasts inhibit satellite cell proliferation during aberrant regeneration of lacerated skeletal muscle

Scientific Reports ◽

10.1038/s41598-020-79771-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Abinaya Sundari Thooyamani ◽

Asok Mukhopadhyay

Keyword(s):

Skeletal Muscle ◽

Muscle Injury ◽

Skeletal Muscle Regeneration ◽

Tissue Architecture ◽

Muscle Fibrosis ◽

Molecular Events ◽

Injury Model ◽

Aberrant Regeneration ◽

Muscle Remodeling

AbstractAberrant regeneration or fibrosis in muscle is the denouement of deregulated cellular and molecular events that alter original tissue architecture due to accumulation of excessive extracellular matrix. The severity of the insult to the skeletal muscle determines the nature of regeneration. Numerous attempts at deciphering the mechanism underlying fibrosis and the subsequent strategies of drug therapies have yielded temporary solutions. Our intent is to understand the interaction between the myofibroblasts (MFs) and the satellite cells (SCs), during skeletal muscle regeneration. We hypothesize that MFs contribute to the impairment of SCs function by exhibiting an antagonistic influence on their proliferation. A modified laceration based skeletal muscle injury model in mouse was utilized to evaluate the dynamics between the SCs and MFs during wound healing. We show that the decline in MFs’ number through inhibition of PDGFRα signaling consequently promotes proliferation of the SCs and exhibits improved skeletal muscle remodeling. We further conclude that in situ administration of PDGFRα inhibitor prior to onset of fibrosis may attenuate aberrant regeneration. This opens new possibility for the early treatment of muscle fibrosis by specific targeting of MFs rather than transplantation of SCs.

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A randomized placebo-controlled clinical trial of Nicotinamide Riboside and Pterostilbene supplementation in experimental muscle injury in elderly subjects

10.1101/2021.10.04.21264504 ◽

2021 ◽

Author(s):

Jonas Brorson Jensen ◽

Ole Lindgaard Dollerup ◽

Andreas Buch Moeller ◽

Tine Borum Billeskov ◽

Emilie Dalbram ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Regeneration ◽

Muscle Injury ◽

Skeletal Muscle Regeneration ◽

Elderly Subjects ◽

Controlled Clinical Trial ◽

Post Injury ◽

Skeletal Muscle Injury ◽

Nicotinamide Riboside ◽

Muscle Work

Background Maintenance and regeneration of functional skeletal muscle are dependent on a sufficient pool of muscle stem cells (MuSCs). During ageing there is a functional decline in this cellular pool which influences the regenerative capacity of skeletal muscle. Preclinical evidence have suggested that Nicotinamide Riboside (NR) and Pterostilbene (PT) can improve muscle regeneration e.g. by increasing MuSC function. The objective of the present study was to investigate if NRPT supplementation promotes skeletal muscle regeneration after muscle injury in elderly humans by improved recruitment of MuSCs. Methods In a randomized, double-blinded, placebo-controlled trial, 32 elderly men and women (55-80 yr) received daily supplementation with either NRPT (1000 mg NR + 200 mg PT) or matched placebo. Two weeks after initiation of supplementation, a skeletal muscle injury was applied in the vastus lateralis part of the quadriceps femoris muscle by electrically induced eccentric muscle work in a dynamometer. Skeletal muscle biopsies were obtained pre, 2h, 2, 8, and 30 days post injury. The main outcome of the study was change in MuSC content 8 days post injury. Results 31 enrolled subjects completed the entire protocol. The muscle work induced a substantial skeletal muscle injury in the study participants and was associated with release of myoglobin and creatine kinase, muscle soreness, tissue edema, and a decrease in muscle strength. MuSC content increased by 107% 8 days post injury (p= 0.0002) but with no effect of NRPT supplementation (p=0.58 for supplementation effect). MuSC proliferation and cell size revealed a large demand for recruitment post injury but was not affected by NRPT. Furthermore, histological analyses of muscle fiber area, internal nuclei and embryonic Myosin Heavy Chain showed no effect of NRPT supplementation. Conclusion Daily supplementation with 1000 mg NR + 200 mg PT is safe but does not improve recruitment of the MuSC pool or other measures of muscle recovery in response to injury or subsequent regeneration in elderly subjects.

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