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

• Published in: Lab on a chip 2023-06, Vol.23 (12), p.2819-2828
• Main Authors: Son, Hyeong-Guk, Hwang, Min-Ho, Lee, Sumin, Kim, An-Gi, Kim, Tae-Won, Kim, Joo-Han, Choi, Hyuk, Jeong, Sehoon
• Format: Article
• Language: English
• Subjects: Degeneration; Differentiation; Humans; Immune system; Infiltration; Intervertebral Disc - metabolism; Intervertebral Disc Degeneration - metabolism; Intervertebral discs; Macrophages; Microphysiological Systems; Monocytes; Nucleus Pulposus - metabolism
• ISSN: 1473-0197; 1473-0189
• DOI: 10.1039/d3lc00032j

Degenerative cascades of the intervertebral disc (IVD) are characterized by the presence of immune cells like monocytes, macrophages, and leukocytes, which contribute to inflammation. Previous in vitro studies on monocyte chemotaxis in the presence of chemical or mechanical stimulation were unable to establish the effects of endogenous stimulating factors from resident IVD cells, or fully understand macrophage and monocyte differentiation pathways in IVD degeneration. Our study simulates monocyte extravasation using a fabricated microfluidic chemotaxis IVD organ-on-a-chip (IVD organ chip), which models the geometry of IVD, chemoattractant diffusion, and infiltration of immune cells. Additionally, the fabricated IVD organ chip mimics stepwise monocyte infiltration and differentiation into macrophages in the degenerative nucleus pulposus (NP) induced by IL-1β. We find that naïve NP cells do not recruit THP-1 monocyte-like cells, but degenerative NP cells recruit and accumulate macrophages through chemo-gradient channels. Furthermore, the differentiated and migrated THP-1 cells show phagocytic activity around inflammatory NP cells. Our in vitro model of monocyte chemotaxis with degenerative NP on an IVD organ chip depicts the sequential processes of monocyte migration/infiltration, monocyte-to-macrophage differentiation, and accumulation. Using this platform to gain a deeper understanding of monocyte infiltration and differentiation processes can provide insights into the pathophysiology of the immune response in degenerative IVD. The intervertebral disc (IVD) organ-on-a-chip is a multi-cellular analytical platform that recapitulates the geometry of the IVD. This bioinspired microsystem mimics monocyte extravasation and enables the study of cell-to-cell paracrine signaling by utilizing chemotaxis.