Department of Medical Sciences, Graduate School of Medicine, Korea University, 148, Gurodong-ro, Guro-gu, Seoul 08308, Korea.
Division of Mechanical and Biomedical Mechatronics, and Materials Science and Engineering, College of and Engineering, Kangwon National University, 1, Kangwondaehak-gil, Chuncheon-si 24341, Korea.
Int J Mol Sci. 2022 Sep 4;23(17):10122. doi: 10.3390/ijms231710122.
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.
椎间盘（IVD）的退变是导致下腰痛的主要原因。IVD 退变的特征是 IVD 细胞分泌的炎症细胞因子和基质降解酶的异常表达。此外，巨噬细胞介导的炎症与 IVD 退变密切相关。然而，巨噬细胞介导的 IVD 炎症的确切病理机制仍不清楚。在这项研究中，我们开发了一种集成了电刺激（ES）阵列的微流控平台，用于研究人髓核（NP）中的巨噬细胞介导的炎症。该平台提供了具有 ES 的多种不同细胞类型的共培养。我们观察到巨噬细胞与 NP 细胞共培养后，白细胞介素（IL）-6（p<0.001）、IL-8（p<0.05）、基质金属蛋白酶（MMP）-1（p<0.05）和 MMP-3（p<0.05）的表达上调，这表明巨噬细胞介导的炎症和明显的迁移特性。我们还证实了在 10 μA 的 ES 下具有抑制作用，因为在这些条件下产生了 IL-6（p<0.05）和 IL-8（p<0.01）。我们的研究结果表明，ES 对不同疾病的退行性炎症有积极影响。因此，微流控电疗平台可以作为体外退变 IVD 炎症模型，并为电疗提供治疗策略。
