Mesenchymal stem cell-derived exosomes (MSC-EXOs) have been identified as promising therapeutic agents for inflammatory conditions, including ulcerative colitis. Hypoxia preconditioning of MSCs enhances the therapeutic potential of their exosomes by modulating their bioactive cargo. In this study, MSCs at passage 4 were preconditioned under hypoxic conditions (1% O2) for 48 h, and the resulting hypoxia-preconditioned MSC-derived exosomes (HpcMSC-EXOs) were investigated as a targeted therapy for colitis. A mouse model of ulcerative colitis was induced using dextran sulfate sodium. HpcMSC-EXOs were administered to evaluate their therapeutic potential in mitigating disease severity. Exosome biodistribution was monitored using DiR labeling, while clinical scores were assessed to determine the extent of disease alleviation. Inflammatory responses in the colon were examined through cytokine analysis, whereas oxidative stress markers and histopathological alterations were investigated to elucidate the effects of hypoxia preconditioning. The results demonstrated that HpcMSC-EXOs efficiently accumulated in the colon and spleen, promoting targeted delivery. Treatment significantly reduced spleen weight, indicating attenuation of systemic inflammation. HpcMSC-EXOs also decreased pro-inflammatory cytokines (IL-17, IL-1β) and enhanced anti-inflammatory cytokines (IL-10, TGF-β), rebalancing the inflammatory microenvironment. In addition, they exhibited potent antioxidant effects by increasing superoxide dismutase activity and reducing lipid peroxidation. Histological analysis and scoring showed marked improvement in colonic architecture, including crypt preservation, reduced infiltration, and enhanced expression of tight junction proteins (ZO-1, E-cadherin). These findings highlight the therapeutic potential of HpcMSC-EXOs in alleviating dextran sulfate sodium-induced colitis through inflammation modulation, oxidative stress reduction, and epithelial barrier restoration. This study underscores the clinical promise of HpcMSC-derived exosomes as a novel treatment for ulcerative colitis.
Alansi et al. (Mon,) studied this question.