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

Min Ho Hwang, Dong Hyun Cho, Seung Min Baek, Jae Won Lee, Jeong Hun Park, Chang Min Yoo, Jae Hee Shin, Hyo Geun Nam, Hyeong Guk Son, Hyun Jung Lim, Han Sang Cho, Hong Joo Moon, Joo Han Kim, Jong Kwang Lee, Hyuk Choi

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number064107
JournalBiomicrofluidics
Volume11
Issue number6
DOIs
Publication statusPublished - 2017 Nov 1

ASJC Scopus subject areas

  • Biomedical Engineering
  • Materials Science(all)
  • Condensed Matter Physics
  • Fluid Flow and Transfer Processes
  • Colloid and Surface Chemistry

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