Human Umbilical Cord Mesenchymal Stem Cells Extricate Bupivacaine-Impaired Skeletal Muscle Function via Mitigating Neutrophil-Mediated Acute Inflammation and Protecting against Fibrosis

Autor: Ching-Chin Tsai, Ching-Jen Wang, Jai-Hong Cheng, Pei-Chin Chuang, Wen-Hong Su, Hung-Chun Fu, Chien-Ming Sheng
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
Neutrophils
medicine.medical_treatment
umbilical cord mesenchymal stem cells
Inflammation
SMAD
Mesenchymal Stem Cell Transplantation
Catalysis
Article
Umbilical Cord
lcsh:Chemistry
Inorganic Chemistry
Mice
Fibrosis
Transforming Growth Factor beta
medicine
Animals
Humans
Physical and Theoretical Chemistry
Muscle
Skeletal
lcsh:QH301-705.5
Molecular Biology
Macrophage inflammatory protein
Spectroscopy
business.industry
Organic Chemistry
Mesenchymal stem cell
fibrosis
skeletal muscle injury
Skeletal muscle
Mesenchymal Stem Cells
General Medicine
medicine.disease
Computer Science Applications
Mice
Inbred C57BL
Cytokine
medicine.anatomical_structure
lcsh:Biology (General)
lcsh:QD1-999
Neutrophil Infiltration
Cancer research
medicine.symptom
business
Transforming growth factor
Signal Transduction
Zdroj: International Journal of Molecular Sciences
Volume 20
Issue 17
International Journal of Molecular Sciences, Vol 20, Iss 17, p 4312 (2019)
ISSN: 1422-0067
Popis: 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&rsquo
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-&gamma
as determined using a Quantibody Mouse Cytokine Array assay. Subsequently, uMSCs noticeably prevented BPVC-accelerated collagen deposition and fibrosis, measured by Masson&rsquo
s trichrome staining. Remarkably, uMSCs attenuated BPVC-induced Transforming growth factor (TGF)-&beta
1 expression, a master regulator of fibrosis. Engrafted uMSCs attenuated TGF-&beta
1 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-&beta
1-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&trade
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.
Databáze: OpenAIRE
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