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国际临床研究杂志

International Journal of Clinical Research

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International Journal of Clinical Research. 2026; 10: (9) ; 10.12208/j.ijcr.20260443 .

SDF-1 preconditioning enhances the therapeutic effect of bone marrow mesenchymal stem cells on ulcerative colitis: An experimental study
SDF-1预处理增强骨髓间充质干细胞治疗溃疡性结肠炎的实验研究

作者： 邓翠1, 郑盛2 *, 杨涓3, 张思敏1, 李姣1

1大理大学临床医学院 云南大理

2大理大学第二附属医院消化内科 云南昆明

3云南大学附属医院消化内科 云南昆明

*通讯作者： 郑盛,单位：大理大学第二附属医院消化内科 云南昆明; ；

引用本文: 邓翠, 郑盛, 杨涓, 张思敏, 李姣 SDF-1预处理增强骨髓间充质干细胞治疗溃疡性结肠炎的实验研究[J]. 国际临床研究杂志, 2026; 10: (9) : 83-92.
Published: 2026/9/10 11:05:56

摘要

目的 本研究探讨基质细胞衍生因子-1（SDF-1）预处理能否通过上调骨髓间充质干细胞（Bone marrow mesenchymal stem cells, BMSCs）表面C‑X‑C型趋化因子受体4（CXCR4）表达，同时改善其归巢能力与免疫调节功能，从而提升溃疡性结肠炎（Ulcerative Colitis, UC）治疗效果。方法 分离、培养并鉴定BALB/c小鼠BMSCs。体外以不同浓度SDF-1（0～200 ng/mL）处理BMSCs，采用Transwell小室和流式细胞术分别检测细胞迁移能力及CXCR4表达水平。将经SDF-1或CXCR4拮抗剂AMD3100预处理的BMSCs与小鼠脾细胞共培养，诱导耐受性树突状细胞（Tol-DC）、M2型巨噬细胞及调节性T细胞（Treg）。体内建立葡聚糖硫酸钠（DSS）诱导的急性UC小鼠模型，随机分为对照组、模型组、BMSCs组、SDF-1-BMSCs组及AMD3100-BMSCs组，经尾静脉输注相应细胞。评估疾病活动指数（DAI）、结肠长度及组织病理学变化；检测肠组织和血清中炎性因子水平；流式细胞术检测脾脏中Tol-DC、M2、Treg比例；CM-DiI标记法观察BMSCs在结肠的归巢情况。结果 SDF-1浓度依赖性地促进BMSCs迁移并上调CXCR4表达，以100 ng/mL效果最佳（P<0.001）。SDF-1预处理显著增强BMSCs诱导脾细胞分化为Tol-DC、M2及Treg的能力，而AMD3100可逆转该效应。体内实验中，与DSS组相比，BMSCs组和SDF-1-BMSCs组小鼠的体重下降、DAI评分和结肠缩短均明显改善。在造模第10天时，SDF-1-BMSCs组小鼠的DAI评分显著低于普通BMSCs组（1.42±0.08比1.92±0.08，P<0.01），结肠长度恢复显著优于普通BMSCs组（8.80±0.27 cm比8.04±0.32 cm，P<0.01），而AMD3100-BMSCs组的改善效果被显著抑制。SDF-1-BMSCs组肠组织和血清中促炎因子（TNF-α、IL-6）水平低于BMSCs组，而抗炎因子（IL-4、IL-10）水平则更高（均P<0.01）。同时，该组脾脏中Tol-DC、M2、Treg比例进一步升高，结肠组织中CM-DiI标记的BMSCs数量明显增多。AMD3100干预后上述增强效应基本消失。结论 SDF-1预处理通过上调CXCR4表达，同步增强BMSCs向炎症结肠的归巢能力及系统性免疫调节功能，从而显著提升对实验性UC的治疗效果。

关键词： 溃疡性结肠炎；间充质干细胞；基质细胞衍生因子-1；归巢；免疫调节

Abstract

Objective This study investigated whether stromal cell-derived factor-1 (SDF-1) pretreatment could enhance both homing and immunomodulatory capacities of bone marrow mesenchymal stem cells (BMSCs) by upregulating C‑X‑C chemokine receptor type 4 (CXCR4) expression, thereby improving the therapeutic efficacy for ulcerative colitis（UC）.
Methods BMSCs were isolated, cultured, and identified from BALB/c mice. In vitro, BMSCs were treated with different concentrations of SDF-1 (0–200 ng/mL). Cell migration ability and CXCR4 expression level were assessed by Transwell assay and flow cytometry, respectively. BMSCs pretreated with SDF-1 or the CXCR4 antagonist AMD3100 were co-cultured with mouse splenocytes to induce tolerogenic dendritic cells (Tol-DCs), M2 macrophages, and regulatory T cells (Tregs). In vivo, an acute UC mouse model was established using dextran sulfate sodium (DSS). Mice were randomly divided into control, DSS, DSS+BMSCs, DSS+SDF-1-BMSCs, and DSS+AMD3100-BMSCs groups, and received corresponding cell infusions via the tail vein. Disease activity index (DAI), colon length, and histopathological changes were evaluated. Inflammatory cytokine levels in intestinal tissue and serum were measured. The proportions of Tol-DCs, M2 macrophages, and Tregs in the spleen were detected by flow cytometry. CM-DiI labeling was used to observe BMSCs homing to the colon.
Results SDF-1 promoted BMSC migration and upregulated CXCR4 expression in a concentration-dependent manner, with the optimal effect at 100 ng/mL (P<0.001). SDF-1 pretreatment significantly enhanced the ability of BMSCs to induce splenocyte differentiation into Tol-DCs, M2 macrophages, and Tregs, which was reversed by AMD3100. In in vivo experiments, compared with the DSS group, the weight loss, DAI score, and colon shortening in mice belonging to the BMSCs group and the SDF-1-BMSCs group were significantly improved. On the 10th day after model establishment, the DAI score of mice in the SDF-1-BMSCs group was significantly lower than that of those in the regular BMSCs group (1.42±0.08 versus 1.92±0.08, P<0.01); moreover, the length of their colon recovered more significantly than in the regular BMSCs group (8.80±0.27 cm versus 8.04±0.32 cm, P<0.01). The improvement effects observed in the AMD3100-BMSCs group, on the other hand, were significantly reduced. The levels of pro-inflammatory cytokines (TNF-α, IL-6) in intestinal tissue and serum were lower, while those of anti-inflammatory cytokines (IL-4, IL-10) were higher in the SDF-1-BMSCs group than in the BMSCs group (all P<0.01). Moreover, the proportions of Tol-DCs, M2 macrophages, and Tregs in the spleen were further increased, and the number of CM-DiI-labeled BMSCs homing to the colon was significantly higher in the SDF-1-BMSCs group. All these enhancing effects were largely abolished by AMD3100 intervention.
Conclusion   SDF-1 pretreatment enhances both the homing ability to the inflamed colon and the systemic immunomodulatory function of BMSCs by upregulating CXCR4 expression, thereby significantly improving the therapeutic efficacy in experimental UC.

Key words： Ulcerative colitis; Mesenchymal stem cells; Stromal cell-derived factor-1; Homing; Immuno-modulation

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