In vitro model of distinct catabolic and inflammatory response patterns of endothelial cells to intervertebral disc cell degeneration

Hwang, Myung Jin; Son, Hyeong Guk; Kim, Joohan; Choi, Hyuk

doi:10.1038/s41598-020-77785-6

Cited by 13 publications

(16 citation statements)

References 40 publications

(55 reference statements)

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“…More recently, electrical stimulation was tested as treatment to modulate IL-1β-mediated catabolism in NP cells ( Kim et al, 2021 ). Additionally, a microfluidic platform was used in a co-culture system of AF, NP, and endothelial cells to investigate IDD development from inflammatory and neurotrophic factors, which could be further developed to examine pain mechanisms in IDD ( Hwang et al, 2020 ; Mainardi et al, 2021 ). The ability to evaluate pain in culture systems of IVD is currently lacking, which is a major issue in translating tissue engineering strategies successfully to clinics ( Isa et al, 2022 ).…”

Section: Research Methods For Exploring the Inflammatory Or Catabolic...mentioning

confidence: 99%

Immuno-Modulatory Effects of Intervertebral Disc Cells

Bermudez-Lekerika

Crump

Tseranidou

et al. 2022

Front. Cell Dev. Biol.

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Low back pain is a highly prevalent, chronic, and costly medical condition predominantly triggered by intervertebral disc degeneration (IDD). IDD is often caused by structural and biochemical changes in intervertebral discs (IVD) that prompt a pathologic shift from an anabolic to catabolic state, affecting extracellular matrix (ECM) production, enzyme generation, cytokine and chemokine production, neurotrophic and angiogenic factor production. The IVD is an immune-privileged organ. However, during degeneration immune cells and inflammatory factors can infiltrate through defects in the cartilage endplate and annulus fibrosus fissures, further accelerating the catabolic environment. Remarkably, though, catabolic ECM disruption also occurs in the absence of immune cell infiltration, largely due to native disc cell production of catabolic enzymes and cytokines. An unbalanced metabolism could be induced by many different factors, including a harsh microenvironment, biomechanical cues, genetics, and infection. The complex, multifactorial nature of IDD brings the challenge of identifying key factors which initiate the degenerative cascade, eventually leading to back pain. These factors are often investigated through methods including animal models, 3D cell culture, bioreactors, and computational models. However, the crosstalk between the IVD, immune system, and shifted metabolism is frequently misconstrued, often with the assumption that the presence of cytokines and chemokines is synonymous to inflammation or an immune response, which is not true for the intact disc. Therefore, this review will tackle immunomodulatory and IVD cell roles in IDD, clarifying the differences between cellular involvements and implications for therapeutic development and assessing models used to explore inflammatory or catabolic IVD environments.

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Section: Research Methods For Exploring the Inflammatory Or Catabolic...mentioning

confidence: 99%

Immuno-Modulatory Effects of Intervertebral Disc Cells

Bermudez-Lekerika

Crump

Tseranidou

et al. 2022

Front. Cell Dev. Biol.

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“…More recently, an IVD co-culture OoC was developed to investigate chemotactic invasion and migration of AF/NP cells and ECs in conditions simulating an inflamed IVD (Hwang et al, 2020). The device, schematized in Figure 2E together with the adopted experimental timeline, is composed of three distinct chambers separated by two rows of posts.…”

Section: Cytokine-based Ivd-on-a-chip Modelsmentioning

confidence: 99%

“…production of IL-6 and -8, VEGF, and MMP-3 was significantly higher in NP cells than in AF cells, under the presence of ECs conditioned medium). While the study gave a first insight into intracellular communications in IVD degeneration, paracrine signaling mechanisms involved in cell communication and migration were not characterized (Hwang et al, 2020). More advanced co-culture OoCs could reveal mechanisms modulating the recruitment of non-IVD cells (immune, endothelial, and neuronal cells) and enable precise targeting of pain mechanisms related to disease progression.…”

Section: Cytokine-based Ivd-on-a-chip Modelsmentioning

confidence: 99%

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Intervertebral Disc-on-a-Chip as Advanced In Vitro Model for Mechanobiology Research and Drug Testing: A Review and Perspective

Mainardi

Cambria

Occhetta

et al. 2022

Front. Bioeng. Biotechnol.

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Discogenic back pain is one of the most diffused musculoskeletal pathologies and a hurdle to a good quality of life for millions of people. Existing therapeutic options are exclusively directed at reducing symptoms, not at targeting the underlying, still poorly understood, degenerative processes. Common intervertebral disc (IVD) disease models still do not fully replicate the course of degenerative IVD disease. Advanced disease models that incorporate mechanical loading are needed to investigate pathological causes and processes, as well as to identify therapeutic targets. Organs-on-chip (OoC) are microfluidic-based devices that aim at recapitulating tissue functions in vitro by introducing key features of the tissue microenvironment (e.g., 3D architecture, soluble signals and mechanical conditioning). In this review we analyze and depict existing OoC platforms used to investigate pathological alterations of IVD cells/tissues and discuss their benefits and limitations. Starting from the consideration that mechanobiology plays a pivotal role in both IVD homeostasis and degeneration, we then focus on OoC settings enabling to recapitulate physiological or aberrant mechanical loading, in conjunction with other relevant features (such as inflammation). Finally, we propose our view on design criteria for IVD-on-a-chip systems, offering a future perspective to model IVD mechanobiology.

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“…Lab-on-a-chip technology, based on microfluidic engineering, has been developed to provide quantitative results similar to the physiological activity of the body in an in vitro model and is potentially applicable for the development of a new platform for various disease studies [15][16][17]. Cell co-culture platforms, based on microfluidics, can be used to analyze multicellular interactions in real-time and can be applied as an experimental tool that simulates the 3D microenvironments in the body.…”

Section: Introductionmentioning

confidence: 99%

Microfluidic Chip with Low Constant-Current Stimulation (LCCS) Platform: Human Nucleus Pulposus Degeneration In Vitro Model for Symptomatic Intervertebral Disc

Kim

Kwon

et al. 2021

Micromachines

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Intervertebral disc (IVD) degeneration is a major cause of low back pain (LBP) in the lumbar spine. This phenomenon is caused by several processes, including matrix degradation in IVD tissues, which is mediated by matrix metalloproteinases (MMPs) and inflammatory responses, which can be mediated by interactions among immune cells, such as macrophages and IVD cells. In particular, interleukin (IL)-1 beta (β), which is a master regulator secreted by macrophages, mediates the inflammatory response in nucleus pulposus cells (NP) and plays a significant role in the development or progression of diseases. In this study, we developed a custom electrical stimulation (ES) platform that can apply low-constant-current stimulation (LCCS) signals to microfluidic chips. Using this platform, we examined the effects of LCCS on IL-1β-mediated inflammatory NP cells, administered at various currents (5, 10, 20, 50, and 100 μA at 200 Hz). Our results showed that the inflammatory response, induced by IL-1β in human NP cells, was successfully established. Furthermore, 5, 10, 20, and 100 μA LCCS positively modulated inflamed human NP cells’ morphological phenotype and kinetic properties. LCCS could affect the treatment of degenerative diseases, revealing the applicability of the LCCS platform for basic research of electroceuticals.

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In vitro model of distinct catabolic and inflammatory response patterns of endothelial cells to intervertebral disc cell degeneration

Cited by 13 publications

References 40 publications

Immuno-Modulatory Effects of Intervertebral Disc Cells

Immuno-Modulatory Effects of Intervertebral Disc Cells

Intervertebral Disc-on-a-Chip as Advanced In Vitro Model for Mechanobiology Research and Drug Testing: A Review and Perspective

Microfluidic Chip with Low Constant-Current Stimulation (LCCS) Platform: Human Nucleus Pulposus Degeneration In Vitro Model for Symptomatic Intervertebral Disc

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