scholarly journals Development of Microfluidic Stretch System for Studying Recovery of Damaged Skeletal Muscle Cells

Micromachines ◽  
2018 ◽  
Vol 9 (12) ◽  
pp. 671 ◽  
Author(s):  
Wanho Kim ◽  
Jaesang Kim ◽  
Hyung-Soon Park ◽  
Jessie Jeon
Keyword(s):  
Skeletal Muscle ◽  
Muscle Injury ◽  
Muscle Fibers ◽  
Movement Control ◽  
Muscle Cells ◽  
Cyclic Stretch ◽  
Intensity Change ◽  
Physical Damage ◽  
Skeletal Muscle Injury

The skeletal muscle occupies about 40% mass of the human body and plays a significant role in the skeletal movement control. Skeletal muscle injury also occurs often and causes pain, discomfort, and functional impairment in daily living. Clinically, most studies observed the recovery phenomenon of muscle by massage or electrical stimulation, but there are limitations on quantitatively analyzing the effects on recovery. Although additional efforts have been made within in vitro biochemical research, some questions still remain for effects of the different cell microenvironment for recovery. To overcome these limitations, we have developed a microfluidic system to investigate appropriate conditions for repairing skeletal muscle injury. First, the muscle cells were cultured in the microfluidic chip and differentiated to muscle fibers. After differentiation, we treated hydrogen peroxide and 18% axial stretch to cause chemical and physical damage to the muscle fibers. Then the damaged muscle fibers were placed under the cyclic stretch condition to allow recovery. Finally, we analyzed the damage and recovery by quantifying morphological change as well as the intensity change of intracellular fluorescent signals and showed the skeletal muscle fibers recovered better in the cyclic stretched condition. In total, our in situ generation of muscle damage and induction recovery platform may be a key system for investigating muscle recovery and rehabilitation.

scholarly journals Tissue-Engineered Human Myobundle System as a Platform for Evaluation of Skeletal Muscle Injury Biomarkers

2020 ◽  
Vol 176 (1) ◽  
pp. 124-136
Author(s):  
Alastair Khodabukus ◽  
Amulya Kaza ◽  
Jason Wang ◽  
Neel Prabhu ◽  
Richard Goldstein ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Injury ◽  
Culture Media ◽  
Contractile Function ◽  
Significant Loss ◽  
Drug Induced ◽  
Skeletal Muscle Injury ◽  
Specificity And Sensitivity ◽  
Novel Biomarkers

Abstract Traditional serum biomarkers used to assess skeletal muscle damage, such as activity of creatine kinase (CK), lack tissue specificity and sensitivity, hindering early detection of drug-induced myopathies. Recently, a novel four-factor skeletal muscle injury panel (MIP) of biomarkers consisting of skeletal troponin I (sTnI), CK mass (CKm), fatty-acid-binding protein 3 (Fabp3), and myosin light chain 3, has been shown to have increased tissue specificity and sensitivity in rodent models of skeletal muscle injury. Here, we evaluated if a previously established model of tissue-engineered functional human skeletal muscle (myobundle) can allow detection of the MIP biomarkers after injury or drug-induced myotoxicity in vitro. We found that concentrations of three MIP biomarkers (sTnI, CKm, and Fabp3) in myobundle culture media significantly increased in response to injury by a known snake venom (notexin). Cerivastatin, a known myotoxic statin, but not pravastatin, induced significant loss of myobundle contractile function, myotube atrophy, and increased release of both traditional and novel biomarkers. In contrast, dexamethasone induced significant loss of myobundle contractile function and myotube atrophy, but decreased the release of both traditional and novel biomarkers. Dexamethasone also increased levels of matrix metalloproteinase-2 and -3 in the culture media which correlated with increased remodeling of myobundle extracellular matrix. In conclusion, this proof-of-concept study demonstrates that tissue-engineered human myobundles can provide an in vitro platform to probe patient-specific drug-induced myotoxicity and performance assessment of novel injury biomarkers to guide preclinical and clinical drug development studies.

Effects of different magnitudes of cyclic stretch on Na+-K+-ATPase in skeletal muscle cells in vitro

2007 ◽  
Vol 212 (2) ◽  
pp. 509-518 ◽  
Author(s):  
Xiao Yuan ◽  
Zhu Lin ◽  
Songjiao Luo ◽  
Guoping Ji ◽  
Changqing Yuan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Cells ◽  
Cyclic Stretch ◽  
Skeletal Muscle Cells

scholarly journals Annexin A1 drives macrophage skewing towards a resolving phenotype to accelerate the regeneration of muscle injury through AMPK activation

2018 ◽  
Author(s):  
Simon McArthur ◽  
Thomas Gobbetti ◽  
Gaëtan Juban ◽  
Thibaut Desgeorges ◽  
Marine Theret ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Injury ◽  
Muscle Fibres ◽  
Annexin A1 ◽  
Skeletal Muscle Injury ◽  
Cellular Processes ◽  
Reparative Process ◽  
Injury And Repair ◽  
Inflammation Resolution

SummaryUnderstanding the circuits that promote an efficient resolution of inflammation is crucial to deciphering the molecular and cellular processes required to promote tissue repair. Macrophages play a central role in the regulation of inflammation, resolution and repair/regeneration. Using a model of skeletal muscle injury and repair, herein we identify Annexin A1 (AnxA1) as the extracellular trigger of macrophage skewing towards a pro-reparative phenotype. Brought into the injured tissue initially by migrated neutrophils, and then over-expressed in infiltrating macrophages, AnxA1 activates FPR2/ALX receptors and the downstream AMPK signalling cascade leading to macrophage skewing, dampening of inflammation and regeneration of muscle fibres. Mice lacking AnxA1 in all cells or in myeloid cells only display a defect in this reparative process.In vitroexperiments recapitulated these properties, with AMPK null macrophages lacking AnxA1-mediated polarization. Collectively, these data identify the AnxA1/FPR2/AMPK axis as a novel pathway in skeletal muscle injury regeneration.

Magnetic Targeting Improves the Therapeutic Efficacy of Microbubble-Mediated Obstructive Thrombus Sonothrombolysis

2019 ◽  
Vol 119 (11) ◽  
pp. 1752-1766 ◽  
Author(s):  
Xiaoqiang Chen ◽  
Weilan Wu ◽  
Shifei Wang ◽  
Jiayuan Zhong ◽  
Nima Moumin Djama ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Flow Velocity ◽  
Blood Flow Velocity ◽  
Muscle Injury ◽  
Magnetic Targeting ◽  
Skeletal Muscle Injury ◽  
The Us

Background Magnetic targeting may help microbubbles (MBs) reach obstructive thrombi and improve the efficacy of MB-mediated sonothrombolysis, but the role of magnetic targeting in MB-mediated sonothrombolysis remains elusive. Objectives We investigate the feasibility and efficacy of magnetically targeted MB-mediated sonothrombolysis for the treatment of obstructive thrombi. Materials and Methods Red and white thromboembolic models were established in vitro and in vivo. The models were randomly assigned to the control, ultrasound plus control MB (US + C-MB), ultrasound plus magnetic MB (US + M-MB), or US + M-MB + recombinant tissue-type plasminogen activator (r-tPA) groups and treated for 30 minutes. The recanalization rate, average blood flow velocity, hindlimb perfusion, and skeletal muscle injury marker levels were recorded. Results The recanalization rate, average blood flow velocity, and hindlimb perfusion in the red and white thromboembolic models were all significantly higher in the US + M-MB and US + M-MB + r-tPA groups than in the control and US + C-MB groups both in vitro and in vivo. Moreover, the levels of the skeletal muscle injury markers were all significantly lower in the US + M-MB and US + M-MB + r-tPA groups than in the other two groups in vivo for both thromboembolic models. However, the thrombolytic effects of red thrombi performed better than those of white thrombi in the US + M-MB + r-tPA group. Conclusion M-MB-mediated sonothrombolysis improves the efficacy of thrombolysis both in vitro and in vivo, and reduces tissue damage in clogging model; thus, this method may serve as a promising approach for treating thrombus-occlusive diseases.

Calcium-independent phospholipase A2 modulates cytosolic oxidant activity and contractile function in murine skeletal muscle cells

2006 ◽  
Vol 100 (2) ◽  
pp. 399-405 ◽  
Author(s):  
Ming C. Gong ◽  
Sandrine Arbogast ◽  
Zhenheng Guo ◽  
Jeremy Mathenia ◽  
Wen Su ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mammalian Cells ◽  
Contractile Function ◽  
Muscle Fibers ◽  
Force Production ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Force Frequency ◽  
Striated Muscles

Phospholipase A2 (PLA2) activity supports production of reactive oxygen species (ROS) by mammalian cells. In skeletal muscle, endogenous ROS modulate the force of muscle contraction. We tested the hypothesis that skeletal muscle cells constitutively express the calcium-independent PLA2 (iPLA2) isoform and that iPLA2 modulates both cytosolic oxidant activity and contractile function. Experiments utilized differentiated C2C12 myotubes and a panel of striated muscles isolated from adult mice. Muscle preparations were processed for measurement of mRNA by real-time PCR, protein by immunoblot, cytosolic oxidant activity by the dichlorofluorescein oxidation assay, and contractile function by in vitro testing. We found that iPLA2 was constitutively expressed by all muscles tested (myotubes, diaphragm, soleus, extensor digitorum longus, gastrocnemius, heart) and that mRNA and protein levels were generally similar among muscles. Selective iPLA2 blockade by use of bromoenol lactone (10 μM) decreased cytosolic oxidant activity in myotubes and intact soleus muscle fibers. iPLA2 blockade also inhibited contractile function of unfatigued soleus muscles, shifting the force-frequency relationship rightward and depressing force production during acute fatigue. Each of these changes could be reproduced by selective depletion of superoxide anions using superoxide dismutase (1 kU/ml). These findings suggest that constitutively expressed iPLA2 modulates oxidant activity in skeletal muscle fibers by supporting ROS production, thereby influencing contractile properties and fatigue characteristics.

scholarly journals Pim1 kinase positively regulates myoblast behaviors and skeletal muscle regeneration

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Yuantong Liu ◽  
Yue Shang ◽  
Zihan Yan ◽  
Hao Li ◽  
Zhen Wang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Muscle Injury ◽  
Myogenic Differentiation ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Adult Skeletal Muscle ◽  
Skeletal Muscle Injury ◽  
Pim1 Kinase

Abstract Adult skeletal muscle regeneration after injury depends on normal myoblast function. However, the intrinsic mechanisms for the control of myoblast behaviors are not well defined. Herein, we identified Pim1 kinase as a novel positive regulator of myoblast behaviors in vitro and muscle regeneration in vivo. Specifically, knockdown of Pim1 significantly restrains the proliferation and accelerates the apoptosis of myoblasts in vitro, indicating that Pim1 is critical for myoblast survival and amplification. Meanwhile, we found that Pim1 kinase is increased and translocated from cytoplasm into nucleus during myogenic differentiation. By using Pim1 kinase inhibitor, we proved that inhibition of Pim1 activity prevents myoblast differentiation and fusion, suggesting the necessity of Pim1 kinase activity for proper myogenesis. Mechanistic studies demonstrated that Pim1 kinase interacts with myogenic regulator MyoD and controls its transcriptional activity, inducing the expression of muscle-specific genes, which consequently promotes myogenic differentiation. Additionally, in skeletal muscle injury mouse model, deletion of Pim1 hinders the regeneration of muscle fibers and the recovery of muscle strength. Taken together, our study provides a potential target for the manipulation of myoblast behaviors in vitro and the myoblast-based therapeutics of skeletal muscle injury.

scholarly journals Stem Cells for the Treatment of Skeletal Muscle Injury

2009 ◽  
Vol 28 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Andres J. Quintero ◽  
Vonda J. Wright ◽  
Freddie H. Fu ◽  
Johnny Huard
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Muscle Injury ◽  
Skeletal Muscle Injury

scholarly journals Modelling the skeletal muscle injury recovery using in vivo contrast-enhanced micro-CT: a proof-of-concept study in a rat model

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Bruno Paun ◽  
Daniel García Leon ◽  
Alex Claveria Cabello ◽  
Roso Mares Pages ◽  
Elena de la Calle Vargas ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Rat Model ◽  
Muscle Injury ◽  
Micro Ct ◽  
Skeletal Muscle Injury ◽  
Monitoring Time ◽  
Contrast Enhanced Ct ◽  
Contrast Enhanced ◽  
Injury Recovery

Abstract Background Skeletal muscle injury characterisation during healing supports trauma prognosis. Given the potential interest of computed tomography (CT) in muscle diseases and lack of in vivo CT methodology to image skeletal muscle wound healing, we tracked skeletal muscle injury recovery using in vivo micro-CT in a rat model to obtain a predictive model. Methods Skeletal muscle injury was performed in 23 rats. Twenty animals were sorted into five groups to image lesion recovery at 2, 4, 7, 10, or 14 days after injury using contrast-enhanced micro-CT. Injury volumes were quantified using a semiautomatic image processing, and these values were used to build a prediction model. The remaining 3 rats were imaged at all monitoring time points as validation. Predictions were compared with Bland-Altman analysis. Results Optimal contrast agent dose was found to be 20 mL/kg injected at 400 μL/min. Injury volumes showed a decreasing tendency from day 0 (32.3 ± 12.0mm3, mean ± standard deviation) to day 2, 4, 7, 10, and 14 after injury (19.6 ± 12.6, 11.0 ± 6.7, 8.2 ± 7.7, 5.7 ± 3.9, and 4.5 ± 4.8 mm3, respectively). Groups with single monitoring time point did not yield significant differences with the validation group lesions. Further exponential model training with single follow-up data (R2 = 0.968) to predict injury recovery in the validation cohort gave a predictions root mean squared error of 6.8 ± 5.4 mm3. Further prediction analysis yielded a bias of 2.327. Conclusion Contrast-enhanced CT allowed in vivo tracking of skeletal muscle injury recovery in rat.

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