Clinical and translational medicine · 2025
Reconstitution of T cell-mediated immunity by umbilical cord-derived mesenchymal stem cells in ulcerative colitis.
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Luo Xiaoying, Deng Jieping, Jiang Xiaoke, Mi Jun, Bai Yangqiu, Zhang Huimin, Li Yalong, Liu Min, Cai Conghui, Li Pengju, Huang Huanrong, Xu Yueping, Qin Yiwen, Mi Yang, Ding Hui, Yang Zhiyu, Wu Yue, Li Zhenjuan, Lan Ling, Zhang Lida, Wang Li, Chen Guobing, Yue Han, Luo Oscar Junhong, Zhang Bingyong
Аннотация
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.
HIGHLIGHTS: UMSCs effectively induce clinical remission in patients with active UC via T cell-mediated immune reconstitution. scRNA-seq analyses further revealed that UMSC therapy suppressed pro-inflammatory features of T cells and alleviated inflammatory responses by inhibiting the interaction of T cells with B and myeloid cells UMSCs suppressed DUOX2-mediated oxidative stress to attenuate DSS-induced colitis by regulating T cell-mediated immunity.
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.
HIGHLIGHTS: UMSCs effectively induce clinical remission in patients with active UC via T cell-mediated immune reconstitution. scRNA-seq analyses further revealed that UMSC therapy suppressed pro-inflammatory features of T cells and alleviated inflammatory responses by inhibiting the interaction of T cells with B and myeloid cells UMSCs suppressed DUOX2-mediated oxidative stress to attenuate DSS-induced colitis by regulating T cell-mediated immunity.