Stem Cells for the Treatment of Skeletal Muscle Injury

Skeletal muscle injury presents a challenging traumatological dilemma, and current therapeutic options remain mediocre. This study was designed to delineate if engraftment of mesenchymal stem cells derived from umbilical cord Wharton’s jelly (uMSCs) could aid in skeletal muscle healing and persuasive molecular mechanisms. We established a skeletal muscle injury model by injection of myotoxin bupivacaine (BPVC) into quadriceps muscles of C57BL/6 mice. Post BPVC injection, neutrophils, the first host defensive line, rapidly invaded injured muscle and induced acute inflammation. Engrafted uMSCs effectively abolished neutrophil infiltration and activation, and diminished neutrophil chemotaxis, including Complement component 5a (C5a), Keratinocyte chemoattractant (KC), Macrophage inflammatory protein (MIP)-2, LPS-induced CXC chemokine (LIX), Fractalkine, Leukotriene B4 (LTB4), and Interferon-γ, as determined using a Quantibody Mouse Cytokine Array assay. Subsequently, uMSCs noticeably prevented BPVC-accelerated collagen deposition and fibrosis, measured by Masson’s trichrome staining. Remarkably, uMSCs attenuated BPVC-induced Transforming growth factor (TGF)-β1 expression, a master regulator of fibrosis. Engrafted uMSCs attenuated TGF-β1 transmitting through interrupting the canonical Sma- And Mad-Related Protein (Smad)2/3 dependent pathway and noncanonical Smad-independent Transforming growth factor beta-activated kinase (TAK)-1/p38 mitogen-activated protein kinases signaling. The uMSCs abrogated TGF-β1-induced fibrosis by reducing extracellular matrix components including fibronectin-1, collagen (COL) 1A1, and COL10A1. Most importantly, uMSCs modestly extricated BPVC-impaired gait functions, determined using CatWalk™ XT gait analysis. This work provides several innovative insights into and molecular bases for employing uMSCs to execute therapeutic potential through the elimination of neutrophil-mediated acute inflammation toward protecting against fibrosis, thereby rescuing functional impairments post injury.

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The Effect of Mesenchymal Stem Cells on Skeletal Muscle Injury

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000496272.43536.94 ◽

2014 ◽

Vol 46 ◽

pp. 923

Author(s):

Patrick Meyer ◽

Stacey Brickson ◽

Ray Vanderby

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Muscle Injury ◽

Skeletal Muscle Injury

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Comparative Study on Bone Marrow-Versus Adipose-Derived Stem Cells on Regeneration and Re-Innervation of Skeletal Muscle Injury in Wistar Rats

Tissue Engineering and Regenerative Medicine ◽

10.1007/s13770-020-00288-y ◽

2020 ◽

Vol 17 (6) ◽

pp. 887-900

Author(s):

Manal H. Moussa ◽

Ghada G. Hamam ◽

Asmaa E. Abd Elaziz ◽

Marwa A. Rahoma ◽

Abeer A. Abd El Samad ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Bone Marrow ◽

Comparative Study ◽

Muscle Injury ◽

Wistar Rats ◽

Adipose Derived Stem Cells ◽

Skeletal Muscle Injury

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P487 The long-term prognostic value of elevated cardiac troponins in patients undergoing major vascular surgery is not influence by renal function or skeletal muscle injury

European Heart Journal ◽

10.1016/s0195-668x(03)93925-x ◽

2003 ◽

Vol 24 (5) ◽

pp. 74

Author(s):

D POLDERMANS

Keyword(s):

Skeletal Muscle ◽

Renal Function ◽

Vascular Surgery ◽

Prognostic Value ◽

Muscle Injury ◽

Skeletal Muscle Injury ◽

Major Vascular Surgery ◽

Cardiac Troponins

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

European Radiology Experimental ◽

10.1186/s41747-020-00163-4 ◽

2020 ◽

Vol 4 (1) ◽

Cited By ~ 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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