Brief report: Successful in vitro culture of rheumatoid arthritis synovial tissue explants at the air-liquid interface

Koji Sakuraba, Kenjiro Fujimura, Yasuharu Nakashima, Ken Okazaki, Jun Ichi Fukushi, Masanobu Ohishi, Akiko Oyamada, Yukio Esaki, Hisaaki Miyahara, Yukihide Iwamoto, Yasunobu Yoshikai, Hisakata Yamada

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Abstract

Objective To establish a method to culture synovial tissue explants from patients with rheumatoid arthritis (RA). Methods Synovial tissue explants obtained from 10 patients with RA were cultured at the air-liquid interface or were submerged in culture medium. As a control, synovial explants were engrafted subcutaneously into SCID mice. The synovial explants were harvested at different time points, and histologic or flow cytometric analysis was performed. Cytokine levels in the culture supernatants were measured by enzyme-linked immunosorbent assay. Infliximab was added to the air-liquid interface culture to evaluate the effect of tumor necrosis factor α blockade on inflammatory cytokine production. Results The histologic features of RA synovitis, including a hyperplastic lining layer and the presence of cellular infiltrate in the sublining layer, were maintained in synovial tissue explants in air-liquid interface culture. In synovial grafts harvested from SCID-HuRAg mice, the cellular infiltrate was well maintained in the sublining, but the lining layer was lost. Viable CD4+ T cells and macrophages were abundant after air-liquid interface culture but were virtually absent after submerged culture. Furthermore, synovial tissue explants in air-liquid interface culture produced interleukin-6 (IL-6) and IL-8 for a prolonged period of time. The addition of infliximab effectively reduced cytokine production. Conclusion RA synovial explants can be maintained for weeks using an air-liquid interface culture. This simple culture system might be useful for analyzing the pathogenesis of RA synovitis and for developing antirheumatic drugs.

Original languageEnglish
Pages (from-to)887-892
Number of pages6
JournalArthritis and Rheumatology
Volume67
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology

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    Sakuraba, K., Fujimura, K., Nakashima, Y., Okazaki, K., Fukushi, J. I., Ohishi, M., Oyamada, A., Esaki, Y., Miyahara, H., Iwamoto, Y., Yoshikai, Y., & Yamada, H. (2015). Brief report: Successful in vitro culture of rheumatoid arthritis synovial tissue explants at the air-liquid interface. Arthritis and Rheumatology, 67(4), 887-892. https://doi.org/10.1002/art.39019