Abstract Background Despite recent therapeutic advances, 30–40% of patients with inflammatory bowel disease (IBD) fail to respond to current treatments. Mesenchymal stem cell (MSC)–based therapies have emerged as a promising option, yet safety and delivery limitations hinder their clinical translation. Extracellular vesicles (EVs), key mediators of paracrine signaling, may offer a safer and more feasible alternative. This study evaluated the efficacy of Tonsil-derived MSCs (TMSCs)-derived EVs (TMSC-EVs) in a Acute murine colitis model. Methods TMSC-EVs were isolated using tangential flow filtration system and characterized by nanoparticle tracking analyzer and transmission electron microscope. C57BL/6 mice were assigned to four groups: Normal control, colitis control (DSS + phosphate-buffered saline PBS), TMSC (DSS+TMSC) and TMSC-EV (DSS+TMSC-EV) groups. Acute colitis was induced with 2.5% DSS for 5 days, followed by 7 days of water (total 12 days). Severity of colitis was measured by disease activity index (DAI), weight loss, and shortening of colon length. Quantitative PCR (qPCR) for cytokines and histologic analysis was performed. In vivo biodistribution of TMSCs and EVs was assessed using an in vivo imaging system (IVIS) at 1 and 12 hours post-injection. Results Compared with the colitis control group, both TMSC and TMSC-EV treatment significantly reduced DAI (P 0.01) and attenuated weight loss (P 0.05). Colon shortening observed in the colitis control group was significantly restored only in the TMSC-EV group (P 0.05), whereas no significant improvement was observed in the TMSC group (P = 0.14). Histologic scores were significantly lower in the TMSC-EV group compared with colitis control group (P 0.01), but not in the TMSCs (P = 0.49). IVIS imaging showed systemic distribution of TMSCs and TMSC-EVs in normal mice, but selective accumulation in the inflamed colon in DSS-induced colitis model, indicating preferential migration to the inflamed sites. Notably, in IVIS, TMSC-EVs infiltrated the mucosal and submucosal layers, which was not observed in TMSC-treated mice, and also demonstrated faster washout from the colon (Figure 1). qPCR analysis showed significant downregulation of pro-inflammatory markers (M1), including MCP-1, IL-1β, iNOS (all P 0.05), while M2 macrophage markers were unchanged in TMSC-EV-treated mice. Conclusion In this study, TMSC-EVs showed superior therapeutic efficacy compared with TMSCs, reflected by greater improvements in histopathologic scores and colon shortening. This enhanced treatment effect could be driven by their ability to suppress key pro-inflammatory cytokines such as IL-1β and MCP-1, and enhanced delivery of inflamed tissue demonstrated by infiltration of TMSC-EVs into colonic tissue in IVIS. Conflict of interest: Ms. Park, So Yeon: No conflict of interest Joo, Yang Hee: No conflict of interest Lee, Hye Sun: No conflict of interest Byeon, Ju Ran: No conflict of interest Choe, A Reum: No conflict of interest Park, Yehyun: No conflict of interest Kim, Seong-Eun: No conflict of interest Jung, Sung-Ae: No conflict of interest Song, Eun Mi: No conflict of interest
Park et al. (Thu,) studied this question.