Abstract
Tonsil-derived mesenchymal stem cells (TMSCs) showed therapeutic effects on acute and chronic murine colitis models, owing to their immunomodulatory properties; therefore, we evaluated enhanced therapeutic effects of TMSCs on a murine colitis model using three-dimensional (3D) culture method. The expression of angiogenic factors, VEGF, and anti-inflammatory cytokines, IL-10, TSG-6, TGF-β, and IDO-1, was significantly higher in the 3D-TMSC-treated group than in the 2D-TMSC-treated group (P < 0.05). At days 18 and 30 after inducing chronic colitis, disease activity index scores were estimated to be significantly lower in the 3D-TMSC-treated group than in the colitis control (P < 0.001 and P < 0.001, respectively) and 2D-TMSC-treated groups (P = 0.022 and P = 0.004, respectively). Body weight loss was significantly lower in the 3D-TMSC-treated group than in the colitis control (P < 0.001) and 2D-TMSC-treated groups (P = 0.005). Colon length shortening was significantly recovered in the 3D-TMSC-treated group compared to that in the 2D-TMSC-treated group (P = 0.001). Histological scoring index was significantly lower in the 3D-TMSC-treated group than in the 2D-TMSC-treated group (P = 0.002). These results indicate that 3D-cultured TMSCs showed considerably higher therapeutic effects in a chronic murine colitis model than those of 2D-cultured TMSCs via increased anti-inflammatory cytokine expression.
Highlights
Tonsil-derived mesenchymal stem cells (TMSCs) showed therapeutic effects on acute and chronic murine colitis models, owing to their immunomodulatory properties; we evaluated enhanced therapeutic effects of TMSCs on a murine colitis model using three-dimensional (3D) culture method
To evaluate the molecular characteristics of 3D-cultured TMSCs, we analyzed the expression of inflammatory and anti-inflammatory cytokines using qRT-PCR and compared them with the results obtained for 2D-cultured TMSCs
We evaluated the therapeutic effects of 3D-cultured TMSCs in the DSS-induced chronic colitis murine model
Summary
Tonsil-derived mesenchymal stem cells (TMSCs) showed therapeutic effects on acute and chronic murine colitis models, owing to their immunomodulatory properties; we evaluated enhanced therapeutic effects of TMSCs on a murine colitis model using three-dimensional (3D) culture method. Histological scoring index was significantly lower in the 3D-TMSC-treated group than in the 2D-TMSC-treated group (P = 0.002) These results indicate that 3D-cultured TMSCs showed considerably higher therapeutic effects in a chronic murine colitis model than those of 2D-cultured TMSCs via increased anti-inflammatory cytokine expression. Immunosuppressive and newly developed biological agents, including anti-tumor necrosis factor α (TNF-α) agents and small molecules such as anti-integrin agent, have been employed for the treatment of IBD, in addition to conventional therapies that involve 5-aminosalicylic acid and corticosteroids, thereby improving the treatment outcomes of IBD Despite these improvements in IBD treatment, up to 40% of patients with IBD failed to show ideal therapeutic r esults[7,8]. Sulfate sodium (DSS)-induced acute and chronic murine colitis models demonstrated therapeutic efficacy in terms of lowering disease activity index (DAI) scores, colon length recovery, and by decreasing the expression of pro-inflammatory c ytokines[14,15]. TMSC-conditioned medium showed similar efficacy as TMSCs in acute and chronic murine colitis models, thereby suggesting that TMSCs exhibit therapeutic effects through the anti-inflammatory mechanism
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