Mesenchymal stem cell exosome (MSCs-exo) is a class of products secreted by mesenchymal stem cells (MSCs) that contain various biologically active substances. MSCs-exo is a promising alternative to MSCs due to their lower immunogenicity and lack of ethical constraints. Ginsenoside Rh2 (Rh2) is a hydrolyzed component of the primary active substance of ginsenosides. Rh2 has a variety of pharmacological functions, including anti-inflammatory, anti-tumor, and antioxidant. Studies have demonstrated that gut microbiota and metabolites are critical in developing rheumatoid arthritis (RA). In this study, we constructed a collagen-induced arthritis (CIA) model in rats. We used MSCs-exo combined with Rh2 to treat CIA rats. To observe the effect of MSCs-exo combined with Rh2 on joint inflammation, rat feces were collected for 16 rRNA amplicon sequencing and untargeted metabolomics analysis. The results showed that the arthritis index score and joint swelling of CIA rats treated with MSCs-exo in combination with Rh2 were significantly lower than those of the model and MSCs-exo alone groups. MSCs-exo and Rh2 significantly ameliorated the disturbed gut microbiota in CIA rats. The regulation of Candidatus_Saccharibacteria and Clostridium_XlVb regulation may be the most critical. Rh2 enhanced the therapeutic effect of MSCs-exo compared with the MSCs-exo -alone group. Furthermore, significant changes in gut metabolites were observed in the CIA rat group, and these differentially altered metabolites may act as messengers for host-microbiota interactions. These differential metabolites were enriched into relevant critical metabolic pathways, revealing possible pathways for host-microbiota interactions.

2024-02-25·Sheng li xue bao : [Acta physiologica Sinica]

[Effects of human umbilical cord mesenchymal stem cells (MSCs)-derived exosomes on pulmonary vascular remodeling in hypoxic pulmonary hypertension].

Article

作者: Wang, Yu-Xiang ; Liu, Hong ; Zhang, Yu-Wei ; Ma, Lan ; Ge, Ri-Li ; Zhang, Qing-Qing

The present study aimed to investigate the effect of human umbilical cord mesenchymal stem cells (MSCs)-derived exosomes (MSCs-Exo) on mice with hypoxic pulmonary hypertension (HPH). MSCs were isolated and cultured from human umbilical cords under aseptic conditions, and exosomes were extracted from the supernatants and identified. Healthy SPF C57BL/6 mice were randomly divided into three groups: normoxic group, hypoxic group, and hypoxic+MSCs-Exo group. Mice in the hypoxic group and the hypoxic+MSCs-Exo group were maintained for 28 d at an equivalent altitude of 5 000 m in a hypobaric chamber to establish HPH mouse model. The mice in the hypoxic+MSCs-Exo group were injected with MSCs-Exo via tail vein before hypoxia and on days 1, 3, 5 and 9 of hypoxia, and the mice in the other two groups were injected with PBS. At the end of the experiment, echocardiography was performed to detect pulmonary arterial acceleration time/pulmonary arterial ejection time ratio (PAAT/PET), right ventricular free wall thickness, and right ventricular hypertrophy index RV/(LV+S). HE staining was performed to observe the lung tissue morphology. EVG staining was performed to observe elastic fiber hyperplasia. Immunohistochemistry was performed to detect α smooth muscle actin (α-SMA) expression in lung tissue. Immunofluorescence staining was used to detect macrophage infiltration in lung tissue. qPCR was performed to detect IL-1β and IL-33 in lung tissue, and cytometric bead array was performed to detect IL-10 secretion. Western blotting was used to detect the M1 macrophage marker iNOS, M2 macrophage marker Arg-1 and IL-33/ST2 pathway proteins in lung tissues. The results showed that hypoxia increased pulmonary artery pressure and pulmonary vascular remodeling, increased macrophage infiltration, IL-1β and IL-33 expression (P < 0.05) and upregulated the IL-33/ST2 pathway (P < 0.05). Compared with the hypoxic group, MSCs-Exo treatment increased PAAT/PET (P < 0.05), decreased right ventricular free wall thickness (P < 0.05), right ventricular hypertrophy index RV/(LV+S) (P < 0.05), α-SMA expression in small pulmonary vessels (P < 0.05), and inflammatory factors including IL-1β and IL-33 expression in lung tissue, however increased IL-10 secretion (P < 0.05). In addition, MSCs-Exo treatment upregulated Arg-1 and downregulated iNOS and IL-33/ST2 (P < 0.05). The results suggest that MSC-Exo may alleviate HPH through their immunomodulatory effects.

2023-05-01·Biomedicine & Pharmacotherapy

Depletion of gut microbiota resistance in 5×FAD mice enhances the therapeutic effect of mesenchymal stem cell-derived exosomes

Article

作者: Yan, Jun ; Mu, Xupeng ; Zhao, Jingtong ; Jiang, Hongyu ; Zhang, Xiaowen ; Liu, Te ; Hou, Xuejia ; Jiang, Jinlan ; Zhang, Fuqiang

Mesenchymal stem cell-derived exosomes (MSCs-exo) can be used for treating Alzheimer's disease (AD) by promoting amyloid-β (Aβ) degradation, modulating immune responses, protecting neurology, promoting axonal growth, and improving cognitive impairment. Increasing evidence suggests that the alteration of gut microbiota is closely related to the occurrence and development of Alzheimer's disease. In this study, we hypothesized that dysbiosis of gut microbiota might limit the therapy of MSCs-exo, and the application of antibiotics would improve the therapy.METHODSIn this original research study, we used MSCs-exo to treat 5 ×FAD mice and fed them antibiotic cocktails for 1 week to detect cognitive ability and neuropathy. The mice's feces were collected to investigate alterations in the microbiota and metabolites.RESULTSThe results revealed that the AD gut microbiota eliminated the therapeutic effect of MSCs-exo, whereas antibiotic modulation of disordered gut microbiota and associated metabolites enhanced the therapeutic effect of MSCs-exo.CONCLUSIONSThese results encourage the research of novel therapeutics to enhance MSCs-exo treatment for AD, which could benefit a broader range of patients with AD.

100 项与 MSCs-derived exosomes(Shanghai Jiao Tong University) 相关的药物交易

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