Session Title: Rheumatoid Arthritis - Animal Models II
Session Type: Abstract Submissions (ACR)
Background/Purpose: We recently have reported that human-derived gingival mesenchymal stem cells (GMSC) have strong capacity to suppress immune responses and T cell-mediated collagen-induced arthritis, however, the precise role and functions of GMSC in bone homeostasis are still unknown. This study was undertaken to determine the effects of GMSCs on osteoclastogenesis in vitro and on bone erosion in vivo in collagen-induced arthritis (CIA).
Methods: Human gingival tissues were gained from discard samples from suffers who underwent dental operation, GMSC were isolated from gingival tissues and cultured in α-MEM with 10% FBS. GMSC and mouse bone marrow derived-CD11b+ cells or human CD14+ cells were co-cultured with various ratios in the presence of 20ng/ml m-CSF and 30ng/ml RANKL. Fibroblast cells have been used for negative control. The osteoclast formation was determined by TRIP staining and numbers of osteoclast formation were calculated in microscope. In addition, GMSCs were adoptively transferred to mice with CIA to assess in vivo effects on disease development and bone erosion, the latter determined by CT scanning. To determine the molecular mechanisms, various inhibitors and antibodies have been added to cell cultures and administrated to CIA mice that had been infused with GMSC.
Results: We showed that GMSCs potently suppressed the genesis and proliferation of osteoclast cells from either mouse CD11b+ cells or human CD14+ cells. We also observed that that GMSC suppress osteoclast cell genesis via CD39 signal in vitro. Adoptive transfer of GMSCs reduced the severity of arthritis and bone erosion in CIA mice. Finally, we show that GMSCs are capable of preventing severity of CIA model via CD39 signals.
Conclusion: Use of GMSCs can treat rheumatoid arthritis and prevent bone erosion.
S. G. Zheng,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/gingival-stem-cells-suppress-osteoclast-formation-and-bone-erosion-in-cia-through-cd39-signal/