Microfluidic Electroceuticals Platform for Therapeutic Strategies of Intervertebral Disc Degeneration: Effects of Electrical Stimulation on Human Nucleus Pulposus Cells under Inflammatory Conditions
The degeneration of an intervertebral disc (IVD) is a major cause of lower back pain. IVD degeneration is characterized by the abnormal expression of inflammatory cytokines and matrix degradation enzymes secreted by IVD cells. In addition, macrophage-mediated inflammation is strongly associated with...
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| Veröffentlicht in: | International journal of molecular sciences 2022-09, Vol.23 (17), p.10122 |
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| creator | Kim, Tae-Won Kim, An-Gi Lee, Kwang-Ho Hwang, Min-Ho Choi, Hyuk |
| description | The degeneration of an intervertebral disc (IVD) is a major cause of lower back pain. IVD degeneration is characterized by the abnormal expression of inflammatory cytokines and matrix degradation enzymes secreted by IVD cells. In addition, macrophage-mediated inflammation is strongly associated with IVD degeneration. However, the precise pathomechanisms of macrophage-mediated inflammation in IVD are still unknown. In this study, we developed a microfluidic platform integrated with an electrical stimulation (ES) array to investigate macrophage-mediated inflammation in human nucleus pulposus (NP). This platform provides multiple cocultures of different cell types with ES. We observed macrophage-mediated inflammation and considerable migration properties via upregulated expression of interleukin (IL)-6 (p < 0.001), IL-8 (p < 0.05), matrix metalloproteinase (MMP)-1 (p < 0.05), and MMP-3 (p < 0.05) in human NP cells cocultured with macrophages. We also confirmed the inhibitory effects of ES at 10 μA due to the production of IL-6 (p < 0.05) and IL-8 (p < 0.01) under these conditions. Our findings indicate that ES positively affects degenerative inflammation in diverse diseases. Accordingly, the microfluidic electroceutical platform can serve as a degenerative IVD inflammation in vitro model and provide a therapeutic strategy for electroceuticals. |
| doi_str_mv | 10.3390/ijms231710122 |
| format | Article |
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IVD degeneration is characterized by the abnormal expression of inflammatory cytokines and matrix degradation enzymes secreted by IVD cells. In addition, macrophage-mediated inflammation is strongly associated with IVD degeneration. However, the precise pathomechanisms of macrophage-mediated inflammation in IVD are still unknown. In this study, we developed a microfluidic platform integrated with an electrical stimulation (ES) array to investigate macrophage-mediated inflammation in human nucleus pulposus (NP). This platform provides multiple cocultures of different cell types with ES. We observed macrophage-mediated inflammation and considerable migration properties via upregulated expression of interleukin (IL)-6 (p < 0.001), IL-8 (p < 0.05), matrix metalloproteinase (MMP)-1 (p < 0.05), and MMP-3 (p < 0.05) in human NP cells cocultured with macrophages. We also confirmed the inhibitory effects of ES at 10 μA due to the production of IL-6 (p < 0.05) and IL-8 (p < 0.01) under these conditions. Our findings indicate that ES positively affects degenerative inflammation in diverse diseases. Accordingly, the microfluidic electroceutical platform can serve as a degenerative IVD inflammation in vitro model and provide a therapeutic strategy for electroceuticals.]]></description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms231710122</identifier><identifier>PMID: 36077518</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Cells, Cultured ; Collagen ; Cytokines ; Cytotoxicity ; Degeneration ; Electric Stimulation ; Electrical stimuli ; Electrodes ; Enzymes ; Humans ; Hydrogels ; Inflammation ; Inflammation - metabolism ; Inflammation - therapy ; Interleukin 6 ; Interleukin 8 ; Interleukin-6 - metabolism ; Interleukin-8 - metabolism ; Intervertebral Disc Degeneration - metabolism ; Intervertebral Disc Degeneration - therapy ; Intervertebral discs ; Low back pain ; Macrophages ; Matrix metalloproteinase ; Matrix metalloproteinases ; Metalloproteinase ; Microfluidics ; Nuclei (cytology) ; Nucleus pulposus ; Nucleus Pulposus - cytology ; Nucleus Pulposus - metabolism ; Protein expression ; Proteins ; Stimulation ; Stromelysin 1</subject><ispartof>International journal of molecular sciences, 2022-09, Vol.23 (17), p.10122</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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IVD degeneration is characterized by the abnormal expression of inflammatory cytokines and matrix degradation enzymes secreted by IVD cells. In addition, macrophage-mediated inflammation is strongly associated with IVD degeneration. However, the precise pathomechanisms of macrophage-mediated inflammation in IVD are still unknown. In this study, we developed a microfluidic platform integrated with an electrical stimulation (ES) array to investigate macrophage-mediated inflammation in human nucleus pulposus (NP). This platform provides multiple cocultures of different cell types with ES. We observed macrophage-mediated inflammation and considerable migration properties via upregulated expression of interleukin (IL)-6 (p < 0.001), IL-8 (p < 0.05), matrix metalloproteinase (MMP)-1 (p < 0.05), and MMP-3 (p < 0.05) in human NP cells cocultured with macrophages. We also confirmed the inhibitory effects of ES at 10 μA due to the production of IL-6 (p < 0.05) and IL-8 (p < 0.01) under these conditions. Our findings indicate that ES positively affects degenerative inflammation in diverse diseases. Accordingly, the microfluidic electroceutical platform can serve as a degenerative IVD inflammation in vitro model and provide a therapeutic strategy for electroceuticals.]]></description><subject>Cells, Cultured</subject><subject>Collagen</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Degeneration</subject><subject>Electric Stimulation</subject><subject>Electrical stimuli</subject><subject>Electrodes</subject><subject>Enzymes</subject><subject>Humans</subject><subject>Hydrogels</subject><subject>Inflammation</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - therapy</subject><subject>Interleukin 6</subject><subject>Interleukin 8</subject><subject>Interleukin-6 - metabolism</subject><subject>Interleukin-8 - metabolism</subject><subject>Intervertebral Disc Degeneration - metabolism</subject><subject>Intervertebral Disc Degeneration - therapy</subject><subject>Intervertebral discs</subject><subject>Low back pain</subject><subject>Macrophages</subject><subject>Matrix metalloproteinase</subject><subject>Matrix metalloproteinases</subject><subject>Metalloproteinase</subject><subject>Microfluidics</subject><subject>Nuclei (cytology)</subject><subject>Nucleus pulposus</subject><subject>Nucleus Pulposus - cytology</subject><subject>Nucleus Pulposus - metabolism</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Stimulation</subject><subject>Stromelysin 1</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkltrFDEUxwdRbK0--ioBX3wZzT0zPgiyXW2hXsD6PGQzJ9ssmck2l0K_oJ_L7G4trRCSA-d3_ueS0zSvCX7PWI8_uM2UKCOKYELpk-aYcEpbjKV6-sA-al6ktMGYMir6580Rk1gpQbrj5s83Z2KwvrjRGbT0YHIMBkp2RvuEfnqdbYgTqhe6vIKot3sf-pWjzrB2kFCw6HzOEG8gZlhF7dGpSwadwhrmGpBdmD-ipbVVeg8fkuz0q4qbit8jqJ6zMukZfS_GQ6m5i9-GVI0F-FpKmUeINZP1epp0DvEWLcI8ul1wetk8s7VeeHX3njS_vywvF2ftxY-v54vPF63hRORWC2BUCiuoZj3nWHS255bBShoiGDej6piSZBRm1UvKmKAKtOKcSY47qzt20nw66G7LaoLRwFzn4IdtdJOOt0PQbnjsmd3VsA43Q8-F5EpUgXd3AjFcF0h5mOqwaoN6hlDSQBWhnZCSyYq-_Q_dhBLn2t6OIrV82eNKtQeqfmNKEex9MQQPuw0ZHm1I5d887OCe_rcS7C-7XryG</recordid><startdate>20220904</startdate><enddate>20220904</enddate><creator>Kim, Tae-Won</creator><creator>Kim, An-Gi</creator><creator>Lee, Kwang-Ho</creator><creator>Hwang, Min-Ho</creator><creator>Choi, Hyuk</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4107-2006</orcidid></search><sort><creationdate>20220904</creationdate><title>Microfluidic Electroceuticals Platform for Therapeutic Strategies of Intervertebral Disc Degeneration: Effects of Electrical Stimulation on Human Nucleus Pulposus Cells under Inflammatory Conditions</title><author>Kim, Tae-Won ; 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IVD degeneration is characterized by the abnormal expression of inflammatory cytokines and matrix degradation enzymes secreted by IVD cells. In addition, macrophage-mediated inflammation is strongly associated with IVD degeneration. However, the precise pathomechanisms of macrophage-mediated inflammation in IVD are still unknown. In this study, we developed a microfluidic platform integrated with an electrical stimulation (ES) array to investigate macrophage-mediated inflammation in human nucleus pulposus (NP). This platform provides multiple cocultures of different cell types with ES. We observed macrophage-mediated inflammation and considerable migration properties via upregulated expression of interleukin (IL)-6 (p < 0.001), IL-8 (p < 0.05), matrix metalloproteinase (MMP)-1 (p < 0.05), and MMP-3 (p < 0.05) in human NP cells cocultured with macrophages. We also confirmed the inhibitory effects of ES at 10 μA due to the production of IL-6 (p < 0.05) and IL-8 (p < 0.01) under these conditions. Our findings indicate that ES positively affects degenerative inflammation in diverse diseases. Accordingly, the microfluidic electroceutical platform can serve as a degenerative IVD inflammation in vitro model and provide a therapeutic strategy for electroceuticals.]]></abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36077518</pmid><doi>10.3390/ijms231710122</doi><orcidid>https://orcid.org/0000-0002-4107-2006</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Cells, Cultured Collagen Cytokines Cytotoxicity Degeneration Electric Stimulation Electrical stimuli Electrodes Enzymes Humans Hydrogels Inflammation Inflammation - metabolism Inflammation - therapy Interleukin 6 Interleukin 8 Interleukin-6 - metabolism Interleukin-8 - metabolism Intervertebral Disc Degeneration - metabolism Intervertebral Disc Degeneration - therapy Intervertebral discs Low back pain Macrophages Matrix metalloproteinase Matrix metalloproteinases Metalloproteinase Microfluidics Nuclei (cytology) Nucleus pulposus Nucleus Pulposus - cytology Nucleus Pulposus - metabolism Protein expression Proteins Stimulation Stromelysin 1 |
| title | Microfluidic Electroceuticals Platform for Therapeutic Strategies of Intervertebral Disc Degeneration: Effects of Electrical Stimulation on Human Nucleus Pulposus Cells under Inflammatory Conditions |
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