Extracellular Vesicles Derived from Epidural Fat-Mesenchymal Stem Cells Attenuate NLRP3 Inflammasome Activation and Improve Functional Recovery After Spinal Cord Injury
Spinal cord injury (SCI) is a devastating event which caused high mortality and morbidity. Recently, nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome has been showed to act a critical t role in the secondly injury phase of SCI. In current study, we aimed to investigate the effe...
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| Veröffentlicht in: | Neurochemical research 2020-04, Vol.45 (4), p.760-771 |
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| creator | Huang, Jiang-Hu Fu, Chun-Hui Xu, Yang Yin, Xiao-Ming Cao, Yong Lin, Fei-Yue |
| description | Spinal cord injury (SCI) is a devastating event which caused high mortality and morbidity. Recently, nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome has been showed to act a critical t role in the secondly injury phase of SCI. In current study, we aimed to investigate the effect and underlying molecular mechanisms of extracellular vesicles derived from epidural fat (EF)- mesenchymal stem cells (MSCs) for the treatment of SCI. Ninety-six Sprague–Dawley rats were used for current study and randomly divided into four groups: sham group, SCI group, SCI + Saline group, SCI + Extracellular vesicles group. Basso‐Beattie‐Bresnahan (BBB) scores was applied to evaluate the neurological functional recovery. Cresyl violet–stained was conducted evaluate the protective effect of EF-MSCs-Extracellular vesicles on lesion volume after SCI. ELISA, immunohistochemistry assay, TUNEL assay and western blotting were conducted to investigate the underlying molecular mechanisms. Our results demonstrated that the administration of EF-MSCs-Extracellular vesicles via tail vein injection improved neurological functional recovery and reduced the lesion volume after SCI. And systemic administration of EF-MSCs-Extracellular vesicles significantly inhibited NLRP3 inflammasome activation and reduced the expression of inflammatory cytokines. Additionally, the expression levels of proapoptotic protein Bax was decreased and antiapoptotic Bcl-2 was upregulated with the treatment of EF-MSCs-Extracellular vesicles after SCI. In summary, in current study, we demonstrated for the first time that the EF-MSCs-Extracellular vesicles can improve neurological functional recovery after SCI, and the underlying molecular mechanisms may partly through the inhibition of NLRP3 inflammasome activation. |
| doi_str_mv | 10.1007/s11064-019-02950-x |
| format | Article |
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Recently, nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome has been showed to act a critical t role in the secondly injury phase of SCI. In current study, we aimed to investigate the effect and underlying molecular mechanisms of extracellular vesicles derived from epidural fat (EF)- mesenchymal stem cells (MSCs) for the treatment of SCI. Ninety-six Sprague–Dawley rats were used for current study and randomly divided into four groups: sham group, SCI group, SCI + Saline group, SCI + Extracellular vesicles group. Basso‐Beattie‐Bresnahan (BBB) scores was applied to evaluate the neurological functional recovery. Cresyl violet–stained was conducted evaluate the protective effect of EF-MSCs-Extracellular vesicles on lesion volume after SCI. ELISA, immunohistochemistry assay, TUNEL assay and western blotting were conducted to investigate the underlying molecular mechanisms. Our results demonstrated that the administration of EF-MSCs-Extracellular vesicles via tail vein injection improved neurological functional recovery and reduced the lesion volume after SCI. And systemic administration of EF-MSCs-Extracellular vesicles significantly inhibited NLRP3 inflammasome activation and reduced the expression of inflammatory cytokines. Additionally, the expression levels of proapoptotic protein Bax was decreased and antiapoptotic Bcl-2 was upregulated with the treatment of EF-MSCs-Extracellular vesicles after SCI. In summary, in current study, we demonstrated for the first time that the EF-MSCs-Extracellular vesicles can improve neurological functional recovery after SCI, and the underlying molecular mechanisms may partly through the inhibition of NLRP3 inflammasome activation.</description><identifier>ISSN: 0364-3190</identifier><identifier>EISSN: 1573-6903</identifier><identifier>DOI: 10.1007/s11064-019-02950-x</identifier><identifier>PMID: 31953741</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adipose Tissue - cytology ; Animals ; Apoptosis ; Apoptosis - drug effects ; BAX protein ; Bcl-2 protein ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Cell activation ; Cell Biology ; Cytokines ; Cytokines - metabolism ; Enzyme-linked immunosorbent assay ; Epidural Space - cytology ; Extracellular Vesicles ; Humans ; Immunohistochemistry ; Inflammasomes ; Inflammasomes - metabolism ; Inflammation ; Injuries ; Lesions ; Male ; Mesenchymal stem cells ; Mesenchymal Stem Cells - cytology ; Molecular modelling ; Morbidity ; Neurochemistry ; Neurology ; Neurosciences ; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism ; Nucleotides ; Original Paper ; Proteins ; Rats, Sprague-Dawley ; Recovery ; Recovery of Function ; Spinal Cord - metabolism ; Spinal Cord - pathology ; Spinal cord injuries ; Spinal Cord Injuries - metabolism ; Spinal Cord Injuries - pathology ; Spinal Cord Injuries - therapy ; Stem cell transplantation ; Stem cells ; Vesicles ; Western blotting</subject><ispartof>Neurochemical research, 2020-04, Vol.45 (4), p.760-771</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020</rights><rights>Neurochemical Research is a copyright of Springer, (2020). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-d3349497a136aec45ccff2e3ba5f5758dbfc9fd12173eaa476fd4d61894796b03</citedby><cites>FETCH-LOGICAL-c375t-d3349497a136aec45ccff2e3ba5f5758dbfc9fd12173eaa476fd4d61894796b03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11064-019-02950-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11064-019-02950-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27922,27923,41486,42555,51317</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31953741$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Jiang-Hu</creatorcontrib><creatorcontrib>Fu, Chun-Hui</creatorcontrib><creatorcontrib>Xu, Yang</creatorcontrib><creatorcontrib>Yin, Xiao-Ming</creatorcontrib><creatorcontrib>Cao, Yong</creatorcontrib><creatorcontrib>Lin, Fei-Yue</creatorcontrib><title>Extracellular Vesicles Derived from Epidural Fat-Mesenchymal Stem Cells Attenuate NLRP3 Inflammasome Activation and Improve Functional Recovery After Spinal Cord Injury</title><title>Neurochemical research</title><addtitle>Neurochem Res</addtitle><addtitle>Neurochem Res</addtitle><description>Spinal cord injury (SCI) is a devastating event which caused high mortality and morbidity. Recently, nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome has been showed to act a critical t role in the secondly injury phase of SCI. In current study, we aimed to investigate the effect and underlying molecular mechanisms of extracellular vesicles derived from epidural fat (EF)- mesenchymal stem cells (MSCs) for the treatment of SCI. Ninety-six Sprague–Dawley rats were used for current study and randomly divided into four groups: sham group, SCI group, SCI + Saline group, SCI + Extracellular vesicles group. Basso‐Beattie‐Bresnahan (BBB) scores was applied to evaluate the neurological functional recovery. Cresyl violet–stained was conducted evaluate the protective effect of EF-MSCs-Extracellular vesicles on lesion volume after SCI. ELISA, immunohistochemistry assay, TUNEL assay and western blotting were conducted to investigate the underlying molecular mechanisms. Our results demonstrated that the administration of EF-MSCs-Extracellular vesicles via tail vein injection improved neurological functional recovery and reduced the lesion volume after SCI. And systemic administration of EF-MSCs-Extracellular vesicles significantly inhibited NLRP3 inflammasome activation and reduced the expression of inflammatory cytokines. Additionally, the expression levels of proapoptotic protein Bax was decreased and antiapoptotic Bcl-2 was upregulated with the treatment of EF-MSCs-Extracellular vesicles after SCI. In summary, in current study, we demonstrated for the first time that the EF-MSCs-Extracellular vesicles can improve neurological functional recovery after SCI, and the underlying molecular mechanisms may partly through the inhibition of NLRP3 inflammasome activation.</description><subject>Adipose Tissue - cytology</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>BAX protein</subject><subject>Bcl-2 protein</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell activation</subject><subject>Cell Biology</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Epidural Space - cytology</subject><subject>Extracellular Vesicles</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Inflammasomes</subject><subject>Inflammasomes - metabolism</subject><subject>Inflammation</subject><subject>Injuries</subject><subject>Lesions</subject><subject>Male</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stem Cells - 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Academic</collection><jtitle>Neurochemical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Jiang-Hu</au><au>Fu, Chun-Hui</au><au>Xu, Yang</au><au>Yin, Xiao-Ming</au><au>Cao, Yong</au><au>Lin, Fei-Yue</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extracellular Vesicles Derived from Epidural Fat-Mesenchymal Stem Cells Attenuate NLRP3 Inflammasome Activation and Improve Functional Recovery After Spinal Cord Injury</atitle><jtitle>Neurochemical research</jtitle><stitle>Neurochem Res</stitle><addtitle>Neurochem Res</addtitle><date>2020-04-01</date><risdate>2020</risdate><volume>45</volume><issue>4</issue><spage>760</spage><epage>771</epage><pages>760-771</pages><issn>0364-3190</issn><eissn>1573-6903</eissn><abstract>Spinal cord injury (SCI) is a devastating event which caused high mortality and morbidity. Recently, nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome has been showed to act a critical t role in the secondly injury phase of SCI. In current study, we aimed to investigate the effect and underlying molecular mechanisms of extracellular vesicles derived from epidural fat (EF)- mesenchymal stem cells (MSCs) for the treatment of SCI. Ninety-six Sprague–Dawley rats were used for current study and randomly divided into four groups: sham group, SCI group, SCI + Saline group, SCI + Extracellular vesicles group. Basso‐Beattie‐Bresnahan (BBB) scores was applied to evaluate the neurological functional recovery. Cresyl violet–stained was conducted evaluate the protective effect of EF-MSCs-Extracellular vesicles on lesion volume after SCI. ELISA, immunohistochemistry assay, TUNEL assay and western blotting were conducted to investigate the underlying molecular mechanisms. Our results demonstrated that the administration of EF-MSCs-Extracellular vesicles via tail vein injection improved neurological functional recovery and reduced the lesion volume after SCI. And systemic administration of EF-MSCs-Extracellular vesicles significantly inhibited NLRP3 inflammasome activation and reduced the expression of inflammatory cytokines. Additionally, the expression levels of proapoptotic protein Bax was decreased and antiapoptotic Bcl-2 was upregulated with the treatment of EF-MSCs-Extracellular vesicles after SCI. In summary, in current study, we demonstrated for the first time that the EF-MSCs-Extracellular vesicles can improve neurological functional recovery after SCI, and the underlying molecular mechanisms may partly through the inhibition of NLRP3 inflammasome activation.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>31953741</pmid><doi>10.1007/s11064-019-02950-x</doi><tpages>12</tpages></addata></record> |
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| subjects | Adipose Tissue - cytology Animals Apoptosis Apoptosis - drug effects BAX protein Bcl-2 protein Biochemistry Biomedical and Life Sciences Biomedicine Cell activation Cell Biology Cytokines Cytokines - metabolism Enzyme-linked immunosorbent assay Epidural Space - cytology Extracellular Vesicles Humans Immunohistochemistry Inflammasomes Inflammasomes - metabolism Inflammation Injuries Lesions Male Mesenchymal stem cells Mesenchymal Stem Cells - cytology Molecular modelling Morbidity Neurochemistry Neurology Neurosciences NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Nucleotides Original Paper Proteins Rats, Sprague-Dawley Recovery Recovery of Function Spinal Cord - metabolism Spinal Cord - pathology Spinal cord injuries Spinal Cord Injuries - metabolism Spinal Cord Injuries - pathology Spinal Cord Injuries - therapy Stem cell transplantation Stem cells Vesicles Western blotting |
| title | Extracellular Vesicles Derived from Epidural Fat-Mesenchymal Stem Cells Attenuate NLRP3 Inflammasome Activation and Improve Functional Recovery After Spinal Cord Injury |
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