Mesenchymal stem cell-derived exosome mitigates colitis <i>via</i> the modulation of the gut metagenomics–metabolomics–farnesoid X receptor axis

Ocansey, Dickson Kofi Wiredu; Zhang, Zhe; Xu, Xiangning; Liu, Lianqin; Amoah, Samuel; Chen, Xiang; Wang, Bo; Zhang, Xu; Mao, Fei

doi:10.1039/d2bm00559j

Cited by 28 publications

(12 citation statements)

References 50 publications

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“…Accordingly, a recent study showed that miR-326 carrying MSCs-derived exosome might enable inhibition of the neddylation process and thereby relieves DSSinduced IBD [205]. Recent reports also have clarified that MSC-derived exosome could improve the gut microbiota composition by substantially supporting the structure of OTUs and colitis-induced reduction in α-diversity, enhancing the frequency of 'healthy' bacteria, attenuating disease-associated bacteria and detrimental functions, and promoting other vital cellular functions [206]. In addition, MSCs-derived exosome could convey miR-378a-3p to downregulate the GATA-binding protein 2 (GATA2) expression, which downregulates aquaporin-4 (AQP4) to block the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway, finally inhibiting the incidence of IBD [207].…”

Section: Application Of Mscs-derived Exosome In Ibdmentioning

confidence: 99%

Therapeutic potential of mesenchymal stem/stromal cells (MSCs)-based cell therapy for inflammatory bowel diseases (IBD) therapy

et al. 2023

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Recently, mesenchymal stem/stromal cells (MSCs) therapy has become an emerging therapeutic modality for the treatment of inflammatory bowel disease (IBD), given their immunoregulatory and pro-survival attributes. MSCs alleviate dysregulated inflammatory responses through the secretion of a myriad of anti-inflammatory mediators, such as interleukin 10 (IL-10), transforming growth factor-β (TGFβ), prostaglandin E2 (PGE2), tumor necrosis factor-stimulated gene-6 (TSG-6), etc. Indeed, MSC treatment of IBD is largely carried out through local microcirculation construction, colonization and repair, and immunomodulation, thus alleviating diseases severity. The clinical therapeutic efficacy relies on to the marked secretion of various secretory molecules from viable MSCs via paracrine mechanisms that are required for gut immuno-microbiota regulation and the proliferation and differentiation of surrounding cells like intestinal epithelial cells (IECs) and intestinal stem cells (ISCs). For example, MSCs can induce IECs proliferation and upregulate the expression of tight junction (TJs)-associated protein, ensuring intestinal barrier integrity. Concerning the encouraging results derived from animal studies, various clinical trials are conducted or ongoing to address the safety and efficacy of MSCs administration in IBD patients. Although the safety and short-term efficacy of MSCs administration have been evinced, the long-term efficacy of MSCs transplantation has not yet been verified. Herein, we have emphasized the illumination of the therapeutic capacity of MSCs therapy, including naïve MSCs, preconditioned MSCs, and also MSCs-derived exosomes, to alleviate IBD severity in experimental models. Also, a brief overview of published clinical trials in IBD patients has been delivered.

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Section: Application Of Mscs-derived Exosome In Ibdmentioning

confidence: 99%

Therapeutic potential of mesenchymal stem/stromal cells (MSCs)-based cell therapy for inflammatory bowel diseases (IBD) therapy

et al. 2023

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“…In our recent studies, we reported downregulated expression of FXR in both IBD patients and dextran sodium sulfate (DSS)-induced IBD mice model, which was accompanied by altered primary bile acid biosynthesis. Treatment of the animal model with mesenchymal stem cell-derived exosomes significantly restored colonic FXR alongside improved gut microbiota metagenomics and metabolomics, resulting in relieving macroscopic and microscopic features of IBD ( Ocansey et al, 2022 ; Xu et al, 2022 ). In the mice model of colitis, the intestines of FXR-deficient mice show a more severe proinflammatory and profibrotic state, accompanied by immune dysfunction.…”

Section: The Progress Of Fxr In Ibdmentioning

confidence: 99%

Farnesoid-X receptor as a therapeutic target for inflammatory bowel disease and colorectal cancer

Zhou

Wang

et al. 2022

Front. Pharmacol.

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Farnesoid-X receptor (FXR), as a nuclear receptor activated by bile acids, is a vital molecule involved in bile acid metabolism. Due to its expression in immune cells, FXR has a significant effect on the function of immune cells and the release of chemokines when immune cells sense changes in bile acids. In addition to its regulation by ligands, FXR is also controlled by post-translational modification (PTM) activities such as acetylation, SUMOylation, and methylation. Due to the high expression of FXR in the liver and intestine, it significantly influences intestinal homeostasis under the action of enterohepatic circulation. Thus, FXR protects the intestinal barrier, resists bacterial infection, reduces oxidative stress, inhibits inflammatory reactions, and also acts as a tumor suppressor to impair the multiplication and invasion of tumor cells. These potentials provide new perspectives on the treatment of intestinal conditions, including inflammatory bowel disease (IBD) and its associated colorectal cancer (CRC). Moreover, FXR agonists on the market have certain organizational heterogeneity and may be used in combination with other drugs to achieve a greater therapeutic effect. This review summarizes current data on the role of FXR in bile acid metabolism, regulation of immune cells, and effects of the PTM of FXR. The functions of FXR in intestinal homeostasis and potential application in the treatment of IBD and CRC are discussed.

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“…MSCs exosomes are nanosized vesicles secreted by mesenchymal stem cells that retain the therapeutic properties of the cells, including genetic material, lipids, and proteins (Lee et al, 2021). For example, MSCs exosomes reshaped the intestinal microbiota composition by significantly increasing the abundance of probiotics, decreasing disease-associated bacteria (Ocansey et al, 2022). MSCs promoted the secretion of exosomal MicroRNA-34a-5p and improved intestinal barrier function through Methyltransferase-like 3/insulin-like growth factor 2 mRNA binding protein 3-mediated pre-miR-34 A m 6 A modification (Li et al, 2022).…”

Section: Stem Cells Therapy Of Radiation Enteritismentioning

confidence: 99%

Pathogenesis and therapy of radiation enteritis with gut microbiota

et al. 2023

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Radiotherapy is widely used in clinic due to its good effect for cancer treatment. But radiotherapy of malignant tumors in the abdomen and pelvis is easy to cause radiation enteritis complications. Gastrointestinal tract contains numerous microbes, most of which are mutualistic relationship with the host. Abdominal radiation results in gut microbiota dysbiosis. Microbial therapy can directly target gut microbiota to reverse microbiota dysbiosis, hence relieving intestinal inflammation. In this review, we mainly summarized pathogenesis and novel therapy of the radiation-induced intestinal injury with gut microbiota dysbiosis and envision the opportunities and challenges of radiation enteritis therapy.

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Mesenchymal stem cell-derived exosome mitigates colitis via the modulation of the gut metagenomics–metabolomics–farnesoid X receptor axis

Abstract: Inflammatory bowel disease (IBD) is associated with chronic gut immune dysregulation and altered microbiome and metabolites composition. Bile acids and their receptors such as the farnesoid X receptor (FXR) form...

Cited by 28 publications

References 50 publications

Therapeutic potential of mesenchymal stem/stromal cells (MSCs)-based cell therapy for inflammatory bowel diseases (IBD) therapy

Therapeutic potential of mesenchymal stem/stromal cells (MSCs)-based cell therapy for inflammatory bowel diseases (IBD) therapy

Farnesoid-X receptor as a therapeutic target for inflammatory bowel disease and colorectal cancer

Pathogenesis and therapy of radiation enteritis with gut microbiota

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