Background/Purpose: The synovial lining tissue consists of fibroblast-like synoviocytes (FLS) and monocyte-derived macrophage-like synoviocytes (MLS) within a self-built meshwork of dense extracellular matrix (ECM) components. FLS are thought to direct ECM synthesis, assembly and degradation. Whether FLS themselves or the ECM network serve as guiding structures for MLS migration is incompletely understood. We studied the dynamics of tissue modeling as well as MLS migratory behavior using a 3D synovial tissue in vitro model.

Methods: Human FLS were prepared from synovial tissues obtained as discarded specimens following joint arthroplasty. CD14+ monocytes (MO) were isolated from peripheral blood. Fluorescently labeled FLS and MO were cultured in spherical extracellular matrix micromasses with an average size of 1.5 mm for up to two weeks. Second harmonic generation was used for the visualization of collagen fibers (ECM). Cell migration was monitored by real-time confocal/multi-photon microscopy.

Results: FLS spontaneously formed a synovial lining-like layer at the surface of the 3D cell culture within 3 days. The first signs of collagen fibers co-localized with FLS clusters and appeared as early as day 1. ECM density increased during the establishment of the lining layer.

The majority (98%) of MO was found to be in close contact with the FLS network with low tendency for migration. On the surface of 3D cultures at the tissue/medium interface a minor fraction of MO displayed directed cell movement with an impressive maximum speed of up to 15 mcm/min. MO migration occurred in intimate contact with FLS but did not necessarily follow individual FLS of the network. Inside the synovial tissue, MO migration followed the FLS network rather than the ECM fibers. For both MO contact with FLS seemed to be more important than contact with the ECM.

Conclusion: The 3D synovial tissue culture system allows for monitoring and analyzing the dynamics of synovial lining modeling. Both, FLS and MO appear to cooperate in the organization of the synovial lining tissue with subtle migration patterns of MO in relation to the organized synovial lining architecture. Ongoing experiments address molecular mechanism(s) of MO – FLS interaction in order to identify potential targets for future therapeutic intervention in arthritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/track-along-monocytes-follow-fibroblast-like-synoviocyte-network-for-movement-and-rest-within-the-synovial-tissue/