脐带间充质干细胞重建溃疡性结肠炎中T细胞介导的免疫

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

作者信息

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

机构信息

Department of Gastroenterology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.

Department of Microbiome Laboratory, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.

出版信息

Clin Transl Med. 2025 Aug;15(8):e70452. doi: 10.1002/ctm2.70452.

DOI:10.1002/ctm2.70452

PMID:40842289

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.

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.

摘要

背景

溃疡性结肠炎（UC）是一种病因不明的慢性肠道炎症性疾病。脐带间充质干细胞（UMSC）是治疗UC的一种潜在方法；然而，其治疗UC的疗效机制仍不清楚。

方法

我们进行了一项为期6个月随访的单臂临床试验，以评估UMSC对中重度左侧UC患者的疗效。26名入组患者接受了两次静脉注射UMSC剂量。治疗前后的结肠活检标本通过单细胞RNA测序（scRNA-seq）进行分析。使用有或无UMSC注射的葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型来描述结肠炎症和T细胞功能。

结果

在临床试验中，治疗2个月和6个月后的临床反应/缓解率分别为80.8/46.2%和75.0/37.5%。内镜和组织学检查显示，应答者接受UMSC治疗后结肠黏膜有改善。scRNA-seq数据显示，UMSC治疗可能通过抑制T细胞与B细胞和髓样细胞的相互作用来抑制T淋巴细胞的促炎特征并减轻炎症反应。在小鼠实验中，UMSC通过调节T细胞介导的免疫抑制DUOX2介导的氧化应激，以减轻DSS诱导的结肠炎。