Reconstitution of T cell-mediated immunity by umbilical cord-derived mesenchymal stem cells in ulcerative colitis

Abstract

Background: Ulcerative colitis (UC) is an agnogenic chronic intestinal inflammatory disease. Umbilical cord-derived mesenchymal stem cell (UMSC) is a potential therapeutic approach against UC; however, the mechanisms underlying their efficacy for UC remain unclear.

Methods: We performed a single-arm clinical trial with 6 months follow-up to assess the efficacy of UMSC in patients with moderate to severe left-sided UC. The 26 enrolled patients were administered two UMSC doses intravenously. Pre- and post-therapy colon biopsy specimens were analysed by single-cell RNA sequencing (scRNA-seq). Dextran sulphate sodium (DSS)-induced colitis mouse models with or without UMSC injection were used to delineate colon inflammation and T cell function.

Results: In the clinical trial, the clinical response/remission rates were 80.8/46.2% and 75.0/37.5% after 2 and 6 months of therapy, respectively. Endoscopic and histological examinations showed improvement of colonic mucosa after UMSC therapy in responders. scRNA-seq data showed that UMSC therapy may suppress pro-inflammatory features of T lymphocytes and alleviate inflammatory responses by inhibiting the interaction of T cells with B and myeloid cells. In the murine experiment, UMSCs suppressed DUOX2-mediated oxidative stress to attenuate DSS-induced colitis by regulating T cell-mediated immunity.

Conclusion: UMSC therapy primarily modulates T cell-mediated immunity to achieve gut mucosal immune reconstitution and maintain mucosal barrier integrity, thereby achieving effective UC recovery.

Keywords

immune regulation / single-cell RNA sequencing / T lymphocyte / ulcerative colitis / umbilical cord-derived mesenchymal stem cell

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