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间质干细胞:猫科动物炎症性肠病的一种新的治疗方法。

Mesenchymal stem cells: a novel therapeutic approach for feline inflammatory bowel disease.

机构信息

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, P.R. China.

College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, P.R. China.

出版信息

Stem Cell Res Ther. 2024 Nov 9;15(1):409. doi: 10.1186/s13287-024-04038-y.

DOI:10.1186/s13287-024-04038-y
PMID:39522034
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11550560/
Abstract

BACKGROUND

Inflammatory bowel disease (IBD) poses a significant and growing global health challenge, affecting both humans and domestic cats. Research on feline IBD has not kept pace with its widespread prevalence in human populations. This study aimed to develop a model of feline IBD by incorporating dextran sulfate sodium (DSS) to evaluate the therapeutic potential of MSCs and to elucidate the mechanisms that enhance their action.

METHODS

We conducted a comprehensive clinical assessment, including magnetic resonance imaging (MRI), endoscopy, and histopathological examination. Additionally, alterations in intestinal microbiota were characterized by 16 S rDNA sequencing, and the influence of MSCs on IBD-related gene expression was investigated through transcriptome analysis.

RESULTS

According to our findings, MSC treatment significantly mitigated DSS-induced clinical manifestations, reduced inflammatory cell infiltration, decreased the production of inflammatory mediators, and promoted mucosal repair. Regarding the intestinal microbiota, MSC intervention effectively corrected the DSS-induced dysbiosis, increasing the presence of beneficial bacteria and suppressing the proliferation of harmful bacteria. Transcriptome analysis revealed the ability of MSCs to modulate various inflammatory and immune-related signaling pathways, including cytokine-cytokine receptor interactions, TLR signaling pathways, and NF-κB pathways.

CONCLUSION

The collective findings indicate that MSCs exert multifaceted therapeutic effects on IBD, including the regulation of intestinal microbiota balance, suppression of inflammatory responses, enhancement of intestinal barrier repair, and modulation of immune responses. These insights provide a solid scientific foundation for employing MSCs as an innovative therapeutic strategy for IBD and pave the way for future clinical explorations.

摘要

背景

炎症性肠病(IBD)是一个重大且日益严重的全球性健康挑战,既影响人类,也影响家猫。关于猫 IBD 的研究并没有跟上其在人类中的广泛流行。本研究旨在通过添加葡聚糖硫酸钠(DSS)来建立猫 IBD 模型,以评估 MSC 的治疗潜力,并阐明增强其作用的机制。

方法

我们进行了全面的临床评估,包括磁共振成像(MRI)、内窥镜检查和组织病理学检查。此外,通过 16S rDNA 测序来描述肠道微生物群的变化,并通过转录组分析来研究 MSC 对 IBD 相关基因表达的影响。

结果

根据我们的发现,MSC 治疗显著减轻了 DSS 诱导的临床症状,减少了炎症细胞浸润,降低了炎症介质的产生,并促进了黏膜修复。关于肠道微生物群,MSC 干预有效地纠正了 DSS 诱导的失调,增加了有益细菌的存在并抑制了有害细菌的增殖。转录组分析显示 MSC 能够调节各种炎症和免疫相关信号通路,包括细胞因子-细胞因子受体相互作用、TLR 信号通路和 NF-κB 通路。

结论

这些研究结果表明,MSC 对 IBD 具有多方面的治疗作用,包括调节肠道微生物群平衡、抑制炎症反应、增强肠道屏障修复和调节免疫反应。这些发现为将 MSC 作为 IBD 的创新治疗策略提供了坚实的科学基础,并为未来的临床探索铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/107e/11550560/98f280dc1a79/13287_2024_4038_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/107e/11550560/98f280dc1a79/13287_2024_4038_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/107e/11550560/6ac28642277a/13287_2024_4038_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/107e/11550560/e14925b4f69c/13287_2024_4038_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/107e/11550560/70e70cd713a1/13287_2024_4038_Fig3_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/107e/11550560/d44363200030/13287_2024_4038_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/107e/11550560/61f97163ee6c/13287_2024_4038_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/107e/11550560/98f280dc1a79/13287_2024_4038_Fig7_HTML.jpg

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