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脂肪间充质干细胞通过影响肠道上皮细胞再生、Wnt 信号通路和 T 细胞免疫来缓解三硝基苯磺酸诱导的大鼠结肠炎。

Adipose-derived mesenchymal stem cells alleviate TNBS-induced colitis in rats by influencing intestinal epithelial cell regeneration, Wnt signaling, and T cell immunity.

机构信息

Department of Gastroenterology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.

Department of Colorectal Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.

出版信息

World J Gastroenterol. 2020 Jul 14;26(26):3750-3766. doi: 10.3748/wjg.v26.i26.3750.

DOI:10.3748/wjg.v26.i26.3750
PMID:32774055
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7383848/
Abstract

BACKGROUND

Conventional Crohn's disease (CD) treatments are supportive rather than curative and have serious side effects. Adipose-derived mesenchymal stem cells (ADSCs) have been gradually applied to treat various diseases. The therapeutic effect and underlying mechanism of ADSCs on CD are still not clear.

AIM

To investigate the effect of ADSC administration on CD and explore the potential mechanisms.

METHODS

Wistar rats were administered with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish a rat model of CD, followed by tail injections of green fluorescent protein (GFP)-modified ADSCs. Flow cytometry, qRT-PCR, and Western blot were used to detect changes in the Wnt signaling pathway, T cell subtypes, and their related cytokines.

RESULTS

The isolated cells showed the characteristics of ADSCs, including spindle-shaped morphology, high expression of CD29, CD44, and CD90, low expression of CD34 and CD45, and osteogenic/adipogenic ability. ADSC therapy markedly reduced disease activity index and ameliorated colitis severity in the TNBS-induced rat model of CD. Furthermore, serum anti-sacchromyces cerevisiae antibody and p-anti-neutrophil cytoplasmic antibody levels were significantly reduced in ADSC-treated rats. Mechanistically, the GFP-ADSCs were colocalized with intestinal epithelial cells (IECs) in the CD rat model. GFP-ADSC delivery significantly antagonized TNBS-induced increased canonical Wnt pathway expression, decreased noncanonical Wnt signaling pathway expression, and increased apoptosis rates and protein level of cleaved caspase-3 in rats. In addition, ADSCs attenuated TNBS-induced abnormal inflammatory cytokine production, disturbed T cell subtypes, and their related markers in rats.

CONCLUSION

Successfully isolated ADSCs show therapeutic effects in CD by regulating IEC proliferation, the Wnt signaling pathway, and T cell immunity.

摘要

背景

传统的克罗恩病（CD）治疗方法是支持性的，而不是治愈性的，并且有严重的副作用。脂肪间充质干细胞（ADSCs）已逐渐应用于治疗各种疾病。ADSCs 治疗 CD 的疗效及其潜在机制尚不清楚。

目的

探讨 ADSC 给药对 CD 的影响，并探讨其潜在机制。

方法

采用 2,4,6-三硝基苯磺酸（TNBS）建立大鼠 CD 模型，尾静脉注射 GFP 标记的 ADSCs。流式细胞术、qRT-PCR 和 Western blot 用于检测 Wnt 信号通路、T 细胞亚群及其相关细胞因子的变化。

结果

分离的细胞表现出 ADSC 的特征，包括梭形形态、高表达 CD29、CD44 和 CD90、低表达 CD34 和 CD45，以及成骨/成脂能力。ADSC 治疗可显著降低疾病活动指数，并改善 TNBS 诱导的 CD 大鼠模型的结肠炎严重程度。此外，ADSC 治疗组大鼠血清抗酿酒酵母抗体和 p-抗中性粒细胞胞质抗体水平明显降低。在机制上，GFP-ADSCs 在 CD 大鼠模型中与肠上皮细胞（IECs）共定位。GFP-ADSC 传递可显著拮抗 TNBS 诱导的经典 Wnt 通路表达增加、非经典 Wnt 信号通路表达减少以及大鼠凋亡率和 cleaved caspase-3 蛋白水平升高。此外，ADSCs 可减轻 TNBS 诱导的大鼠异常炎症细胞因子产生、T 细胞亚群及其相关标志物紊乱。

结论

成功分离的 ADSC 通过调节 IEC 增殖、Wnt 信号通路和 T 细胞免疫，对 CD 具有治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7325/7383848/b200d9d3b35c/WJG-26-3750-g007.jpg
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本文引用的文献

1
The state of the art on treatment of Crohn's disease.克罗恩病治疗的最新进展。
J Gastroenterol. 2018 Sep;53(9):989-998. doi: 10.1007/s00535-018-1479-6. Epub 2018 Jul 6.
2
Comparative Analysis between the In Vivo Biodistribution and Therapeutic Efficacy of Adipose-Derived Mesenchymal Stromal Cells Administered Intraperitoneally in Experimental Colitis.腹腔内注射脂肪来源间充质基质细胞治疗实验性结肠炎的体内分布和疗效比较分析。
Int J Mol Sci. 2018 Jun 23;19(7):1853. doi: 10.3390/ijms19071853.
3
Mesenteric Adipose-derived Stromal Cells From Crohn's Disease Patients Induce Protective Effects in Colonic Epithelial Cells and Mice With Colitis.
Bioact Mater. 2024 Mar 1;36:112-125. doi: 10.1016/j.bioactmat.2024.02.023. eCollection 2024 Jun.
4
Mesenchymal Stem Cells Ameliorate DSS-Induced Experimental Colitis by Modulating the Gut Microbiota and MUC-1 Pathway.间充质干细胞通过调节肠道微生物群和MUC-1途径改善右旋糖酐硫酸钠诱导的实验性结肠炎。
J Inflamm Res. 2023 May 11;16:2023-2039. doi: 10.2147/JIR.S402592. eCollection 2023.
5
Investigation of distribution of GSK-3β signal pathway by age groups in cases of ulcerative colitis.研究溃疡性结肠炎患者中 GSK-3β 信号通路的分布与年龄组的关系。
Rom J Morphol Embryol. 2023 Jan-Mar;64(1):57-63. doi: 10.47162/RJME.64.1.07.
6
Therapeutic potential of mesenchymal stem/stromal cells (MSCs)-based cell therapy for inflammatory bowel diseases (IBD) therapy.间充质干细胞（MSCs）为基础的细胞疗法治疗炎症性肠病（IBD）的治疗潜力。
Eur J Med Res. 2023 Jan 27;28(1):47. doi: 10.1186/s40001-023-01008-7.
7
Immunomodulatory Mechanisms of Mesenchymal Stem Cells and Their Potential Clinical Applications.间充质干细胞的免疫调节机制及其潜在的临床应用。
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8
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9
Crosstalk between adipose tissue and the microbiota-gut-brain axis in metabolic diseases.代谢疾病中脂肪组织与微生物群-肠-脑轴的串扰。
Int J Biol Sci. 2022 Feb 7;18(4):1706-1723. doi: 10.7150/ijbs.68786. eCollection 2022.
10
Propofol suppresses adipose-derived stem cell progression via PI3K/AKT-Wnt signaling pathway.丙泊酚通过 PI3K/AKT-Wnt 信号通路抑制脂肪来源干细胞的进展。
BMC Anesthesiol. 2022 Mar 9;22(1):65. doi: 10.1186/s12871-022-01603-x.
克罗恩病患者肠系膜脂肪来源的基质细胞对结肠上皮细胞和结肠炎小鼠具有保护作用。
Cell Mol Gastroenterol Hepatol. 2018 Feb 8;6(1):1-16. doi: 10.1016/j.jcmgh.2018.02.001. eCollection 2018.
4
Wnt signaling in development and tissue homeostasis.Wnt 信号在发育和组织稳态中的作用。
Development. 2018 Jun 8;145(11):dev146589. doi: 10.1242/dev.146589.
5
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Z Rheumatol. 2019 Feb;78(1):82-88. doi: 10.1007/s00393-018-0450-5.
6
Local Mesenchymal Stem Cell Therapy in Experimentally Induced Colitis in the Rat.局部间充质干细胞疗法对大鼠实验性结肠炎的治疗作用
Int J Stem Cells. 2018 May 30;11(1):39-47. doi: 10.15283/ijsc17074.
7
Mesenteric injection of adipose-derived mesenchymal stem cells relieves experimentally-induced colitis in rats by regulating Th17/Treg cell balance.肠系膜注射脂肪源性间充质干细胞通过调节Th17/Treg细胞平衡缓解大鼠实验性结肠炎。
Am J Transl Res. 2018 Jan 15;10(1):54-66. eCollection 2018.
8
Biological characteristics of human menstrual blood-derived endometrial stem cells.人月经血来源的子宫内膜干细胞的生物学特性。
J Cell Mol Med. 2018 Mar;22(3):1627-1639. doi: 10.1111/jcmm.13437. Epub 2017 Dec 26.
9
Extrinsic control of Wnt signaling in the intestine.肠道中Wnt信号通路的外在调控
Differentiation. 2017 Sep-Oct;97:1-8. doi: 10.1016/j.diff.2017.08.003. Epub 2017 Aug 5.
10
Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities.Wnt/β-连环蛋白信号通路、疾病与新兴治疗模式。
Cell. 2017 Jun 1;169(6):985-999. doi: 10.1016/j.cell.2017.05.016.