12.2.3 - Modulation of Inflamed Synovium and its Residing Macrophages Improves in vitro Migration of Mesenchymal Stromal Cells
- M. Wesdorp (Rotterdam, NL)
- M. Wesdorp (Rotterdam, NL)
- S. Capar (Rotterdam, NL)
- K. Sivasubramaniyan (Rotterdam, NL)
- G. Van Osch (Rotterdam, NL)
- Y. Bastiaansen-Jenniskens (Rotterdam, NL)
Abstract
Purpose
Therapeutic solutions aiming to stimulate endogenous repair of osteochondral defects by using scaffolds or hydrogels are emerging. To achieve good integrative repair, mesenchymal stromal cells from the underlying bone marrow (BMSCs) should migrate into the hydrogel/scaffold and deposit extracellular matrix. Osteochondral defects are often accompanied by synovial inflammation. We investigated how synovial inflammation influences BMSC migration, and whether modulation of inflammation improves migration.
Methods and Materials
Osteoarthritic synovial tissue explants were cultured with/without 1 µM triamcinolone acetonide (TAA) for 24 hours to obtain synovium conditioned medium (SCM). The effect of 6 SCM donors on migration of passage 3 BMSCs was examined in a boyden chamber assay. Inflammation of the synovial explants was assessed with gene expression analysis and flow cytometry of synovial macrophages. Human peripheral blood monocytes were stimulated with TNF-α/IFN-γ towards pro-inflammatory macrophages, with IL-4 towards repair macrophages, and with IL-10 towards anti-inflammatory macrophages and their conditioned medium was used to assess BMSC migration on a collagen gel.
Results
SCM resulted in a donor dependent increase in MSC migration. Modulation of synovial inflammation with TAA significantly decreased expression of TNFA, IL1B and IL6, genes associated with inflammation, and increased gene expression of CD163, associated with anti-inflammatory macrophages, in synovial tissue explants. The percentage of CD14+CD80+(p<0.001) or CD14+CD86+(p<0.001) pro-inflammatory macrophages was lower in TAA-treated samples, whereas the percentage of CD14+CD163+ [KS1] anti-inflammatory macrophages was higher(p<0.001) than without TAA. Modulation of synovial inflammation with TAA resulted in a 1.5-fold increase(p<0.01) in migration. Moreover, BMSC migration in collagen gel increased 2.5-fold(p<0.001) in response to medium conditioned by repair macrophages, and 2.3-fold(p<0.01) by anti-inflammatory macrophages. Migration was unaffected by pro-inflammatory macrophage CM.
Conclusion
Decreased synovial inflammation increased BMSC migration. Modulation of inflammation, and macrophage phenotype in synovium using TAA seems promising to enhance BMSC migration. This knowledge could be used in approaches stimulating endogenous repair of osteochondral defects.