Microfluidic Electroceuticals Platform for Therapeutic Strategies of Intervertebral Disc Degeneration: Effects of Electrical Stimulation on Human Nucleus Pulposus Cells under Inflammatory Conditions

被引:6
作者
Kim, Tae-Won [1 ]
Kim, An-Gi [1 ]
Lee, Kwang-Ho [2 ]
Hwang, Min-Ho [1 ]
Choi, Hyuk [1 ]
机构
[1] Korea Univ, Grad Sch Med, Dept Med Sci, 148 Gurodong Ro, Seoul 08308, South Korea
[2] Kangwon Natl Univ, Div Mech & Biomed Mechatron & Mat Sci & Engn, Coll & Engn, 1 Kangwondaehak Gil, Chuncheon Si 24341, South Korea
基金
新加坡国家研究基金会;
关键词
intervertebral disc degeneration; microfluidics; electrical stimulation; nucleus pulposus; macrophages; inflammation; electroceuticals; ANNULUS FIBROSUS CELLS; TISSUE; LOCALIZATION; GROWTH;
D O I
10.3390/ijms231710122
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu A 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.
引用
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页数:14
相关论文
共 46 条
[1]   The expression of metalloproteinases in the lumbar disc correlates strongly with Pfirrmann MRI grades in lumbar spinal fusion patients [J].
Aripaka, Sanjay S. ;
Bech-Azeddine, Rachid ;
Jorgensen, Louise M. ;
Mikkelsen, Jens D. .
BRAIN AND SPINE, 2022, 2
[2]  
Balint R, 2013, TISSUE ENG PART B-RE, V19, P48, DOI [10.1089/ten.teb.2012.0183, 10.1089/ten.TEB.2012.0183]
[3]   How membrane proteins sense voltage [J].
Bezanilla, Francisco .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2008, 9 (04) :323-332
[4]   Electrical stimulation as a novel tool for regulating cell behavior in tissue engineering [J].
Chen, Cen ;
Bai, Xue ;
Ding, Yahui ;
Lee, In-Seop .
BIOMATERIALS RESEARCH, 2019, 23 (01)
[5]   Modulation of the In Vivo Inflammatory Response by Pro- Versus Anti-Inflammatory Intervertebral Disc Treatments [J].
Cunha, Carla ;
Teixeira, Graciosa Q. ;
Ribeiro-Machado, Claudia ;
Pereira, Catarina L. ;
Ferreira, Joana R. ;
Molinos, Maria ;
Santos, Susana G. ;
Barbosa, Mario A. ;
Goncalves, Raquel M. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (05)
[6]   The inflammatory response in the regression of lumbar disc herniation [J].
Cunha, Carla ;
Silva, Ana J. ;
Pereira, Paulo ;
Vaz, Rui ;
Goncalves, Raquel M. ;
Barbosa, Mario A. .
ARTHRITIS RESEARCH & THERAPY, 2018, 20
[7]   Dynamic changes in traction forces with DC electric field in osteoblast-like cells [J].
Curtze, S ;
Dembo, M ;
Miron, M ;
Jones, DB .
JOURNAL OF CELL SCIENCE, 2004, 117 (13) :2721-2729
[8]   Transcutaneous electrical nerve stimulation reduces pain, fatigue and hyperalgesia while restoring central inhibition in primary fibromyalgia [J].
Dailey, Dana L. ;
Rakel, Barbara A. ;
Vance, Carol G. T. ;
Liebano, Richard E. ;
Amrit, Anand S. ;
Bush, Heather M. ;
Lee, Kyoung S. ;
Lee, Jennifer E. ;
Sluka, Kathleen A. .
PAIN, 2013, 154 (11) :2554-2562
[9]   Influence of macrophage infiltration of herniated disc tissue on the production of matrix metalloproteinases leading to disc resorption [J].
Doita, M ;
Kanatani, T ;
Ozaki, T ;
Matsui, N ;
Kurosaka, M ;
Yoshiya, S .
SPINE, 2001, 26 (14) :1522-1527
[10]   Intervertebral Disk Degeneration and Repair [J].
Dowdell, James ;
Erwin, Mark ;
Choma, Theodoe ;
Vaccaro, Alexander ;
Iatridis, James ;
Cho, Samuel K. .
NEUROSURGERY, 2017, 80 (03) :S46-S54