Chronic inflammation-induced senescence impairs immunomodulatory properties of synovial fluid mesenchymal stem cells in rheumatoid arthritisopen access
- Lee, Hyeon-Jeong; Lee, Won-Jae; Hwang, Sun-Chul; Choe, Yongho; Kim, Saetbyul; Bok, Eunyeong; Lee, Sangyeob; Kim, Seung-Joon; Kim, Hyun-Ok; Ock, Sun-A; Noh, Hae-Sook; Rho, Gyu-Jin; Lee, Sang-Il; Lee, Sung-Lim
- Issue Date
- Mesenchymal stem cell-derived from the patient; Rheumatoid arthritis; Duration of inflammatory disease; Immunomodulation; Cellular senescence
- STEM CELL RESEARCH & THERAPY, v.12, no.1
- Journal Title
- STEM CELL RESEARCH & THERAPY
- Background: Although the immunomodulatory properties of mesenchymal stem cells (MSCs) have been highlighted as a new therapy for autoimmune diseases, including rheumatoid arthritis (RA), the disease-specific characteristics of MSCs derived from elderly RA patients are not well understood. Methods: We established MSCs derived from synovial fluid (SF) from age-matched early (average duration of the disease: 1.7 years) and long-standing (average duration of the disease: 13.8 years) RA patients (E-/L-SF-MSCs) and then analyzed the MSC characteristics such as stemness, proliferation, cellular senescence, in vitro differentiation, and in vivo immunomodulatory properties. Results: The presence of MSC populations in the SF from RA patients was identified. We found that L-SF-MSCs exhibited impaired proliferation, intensified cellular senescence, reduced immunomodulatory properties, and attenuated anti-arthritic capacity in an RA animal model. In particular, E-SF-MSCs demonstrated cellular senescence progression and attenuated immunomodulatory properties similar to those of L-SF-MSC in an RA joint-mimetic milieu due to hypoxia and pro-inflammatory cytokine exposure. Due to a long-term exposure to the chronic inflammatory milieu, cellular senescence, attenuated immunomodulatory properties, and the loss of anti-arthritic potentials were more often identified in SF-MSCs in a long-term RA than early RA. Conclusion: We conclude that a chronic RA inflammatory milieu affects the MSC potential. Therefore, this work addresses the importance of understanding MSC characteristics during disease states prior to their application in patients.
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- 수의과대학 > Department of Veterinary Medicine > Journal Articles
- College of Medicine > Department of Medicine > Journal Articles
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