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Spine-on-a-chip: Human annulus fibrosus degeneration model for simulating the severity of intervertebral disc degeneration

The aetiology of intervertebral disc (IVD) degeneration accompanied by low back pain (LBP) is largely unknown, and there are no effective fundamental therapies. Symptomatic IVD is known to be associated with nerve root compression. However, even in the absence of nerve compression, LBP occurs in pat...

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Published in:Biomicrofluidics 2017-11, Vol.11 (6), p.064107-064107
Main Authors: Hwang, Min Ho, Cho, Dong Hyun, Baek, Seung Min, Lee, Jae Won, Park, Jeong Hun, Yoo, Chang Min, Shin, Jae Hee, Nam, Hyo Geun, Son, Hyeong Guk, Lim, Hyun Jung, Cho, Han Sang, Moon, Hong Joo, Kim, Joo Han, Lee, Jong Kwang, Choi, Hyuk
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Language:English
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Summary:The aetiology of intervertebral disc (IVD) degeneration accompanied by low back pain (LBP) is largely unknown, and there are no effective fundamental therapies. Symptomatic IVD is known to be associated with nerve root compression. However, even in the absence of nerve compression, LBP occurs in patients with IVD degeneration. We hypothesize that this phenomenon is associated with a concentration of pro-inflammatory cytokines such as interleukin (IL)-1β and tumour necrosis factor-alpha (TNF-α), which can lead to altered histologic features and cellular phenotypes observed during IVD degeneration. This study investigated the effects of the concentration of IL-1β and macrophage derived soluble factor including IL-1β and TNF-α on the painful response of human annulus fibrosus (AF) cells using a newly developed spine-on-a-chip. Human AF cells were treated with a range of concentrations of IL-1β and macrophage soluble factors. Our results show that increasing the concentration of inflammatory initiator caused modulated expression of pain-related factors, angiogenesis molecules, and catabolic enzymes. Furthermore, accumulated macrophage derived soluble factors resulted in morphological changes in human AF cells and kinetic alterations such as velocity, dendritic length, cell area, and growth rate, similar to that reported within degenerative IVD. Thus, a better understanding of the relationships between molecular and kinetic alterations can provide fundamental information regarding the pathology of IVD degenerative progression.
ISSN:1932-1058
1932-1058
DOI:10.1063/1.5005010