Intervertebral disc organ-on-a-chip: an innovative model to study monocyte extravasation during nucleus pulposus

Hyeong-Guk Son1, Min-Ho Hwang1, Sumin Lee2,3

  • 1Department of Medical Sciences, Graduate School of Medicine, Korea University, 80, Guro-dong, Guro-gu, Seoul 152703, South Korea. hyuk76@korea.ac.kr.

Lab on a Chip
|May 22, 2023
PubMed

Insights

Degenerative disc disease involves immune cells. A new IVD organ chip shows how monocytes infiltrate, differentiate into macrophages, and accumulate in damaged disc tissue, offering insights into inflammation.

Area of Science:

  • Biomedical Engineering
  • Immunology
  • Regenerative Medicine

Background:

  • Intervertebral disc (IVD) degeneration involves immune cell infiltration, including monocytes and macrophages, contributing to inflammation.
  • Previous in vitro models lacked the ability to study endogenous factors influencing monocyte chemotaxis and macrophage differentiation within the IVD microenvironment.

Purpose of the Study:

  • To develop and utilize a novel microfluidic IVD organ-on-a-chip model to simulate monocyte extravasation and differentiation in degenerative IVD.
  • To investigate the role of nucleus pulposus (NP) cells in recruiting and differentiating monocytes into macrophages.

Main Methods:

  • Fabrication of a microfluidic IVD organ chip mimicking IVD geometry, chemoattractant diffusion, and immune cell infiltration.
  • Co-culture of THP-1 monocyte-like cells with naive and IL-1β-induced degenerative NP cells within the IVD organ chip.
  • Assessment of monocyte recruitment, infiltration, differentiation into macrophages, and phagocytic activity.

Main Results:

  • Degenerative NP cells, but not naive NP cells, recruited and accumulated THP-1 monocyte-like cells via chemo-gradient channels.
  • The IVD organ chip successfully modeled stepwise monocyte infiltration and differentiation into macrophages in response to IL-1β.
  • Differentiated THP-1 cells exhibited phagocytic activity towards inflammatory NP cells.

Conclusions:

  • The IVD organ chip provides a robust in vitro platform to study immune cell dynamics in degenerative IVD.
  • This model elucidates the sequential processes of monocyte migration, differentiation, and accumulation in the context of IVD degeneration.
  • Findings offer insights into the immunopathology of degenerative disc disease and potential therapeutic targets.

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