Project description:Mesenchymal stem cell-derived exosomes (MSC-Exos), noted for their minimal immunogenicity and robust immunomodulatory potential, have emerged as key regulators of immune cell fate. Nevertheless, a comprehensive understanding of their global impact on human NK cell proliferation and effector function remains elusive. In this study, we employed a standardized ex vivo expansion and exosome-priming system to systematically evaluate the regulatory effects of MSC-Exos on peripheral blood-derived NK cells via flow cytometry, cytotoxicity assays, single-cell transcriptomics, and proteomic profiling. Proteomic profiling identified an enrichment of FcγR-related signaling components within MSC-Exos, suggesting a potential role in enhancing antibody-dependent cellular cytotoxicity (ADCC).Collectively, our findings demonstrate that MSC-Exos bolster NK cell expansion and effector maturation through coordinated immuno-metabolic reprogramming, offering a strategic approach to enhancing the therapeutic efficacy of NK cell-based immunotherapies.
Project description:Mesenchymal stem cell (MSC)-derived exosomes had been reported to be a prospective candidate in accelerating diabetic wound healing. Hence, this study intended to explore whether exosomes originating from the human umbilical cord MSC (hucMSC) could display a superior proangiogenic effect on diabetic wound repair and its underlying molecular mechanism.
Project description:It is known that antler stem cell extract has an inhibitory effect on glioma growth. Therefore, it is speculated that antler stem cell-derived exosomes (ASC-Exos) can be used as a new drug carrier for the treatment of glioma. Due to the limitation of exosome sources, we constructed a 3D culture system to harvest more exosomes. In this experiment, compared with the 2D-ASC-Exos obtained from the traditional 2D culture, the 3D-ASC-Exos obtained from our constructed 3D culture system were concentrated nearly 30 times in the culture medium volume, which was more convenient for subsequent purification. The two forms of ASC-Exos had similar morphologies and surface markers, but 3D-ASC-Exos were enriched with more miRNAs related to tumor suppression. In vitro experiments demonstrated that 3D-ASC-exosomes loaded with temozolomide (TMZ) inhibited the proliferation, migration and invasion abilities of glioma cells and promoted the apoptosis of glioma cells. The vivo tumor-bearing mouse model demonstrated that 3D-ASC-Exos loaded with TMZ exerted tumor-suppressive effects by inhibiting tumor growth and promoting tumor apoptosis. Meanwhile, the treatment with 3D-ASC-Exos loaded with TMZ caused no damage to the various tissues and organs of mice compared with the TMZ group. In conclusion, 3D-ASC-Exos can be used as a novel drug carrier for the treatment of glioma.
Project description:To determine the key mediators responsible for the anti-angiogenic activity of MSC-exos, we performed transcriptome profiling using the Agilent Human ceRNA Microarray for HUVECs stimulated by H2O2 and cocultured with MSC-exos or not.
Project description:Conventional treatments for inflammatory bowel disease (IBD) have multiple potential side effects. Therefore, alternative treatments are desperately needed. In the present study, we proposed a new therapeutic tool for the treatment of IBD in murine pre-clinical models by using MSC-Exos. We demonstrated that the infused MSC-Exos are immunotolerated by the host, which is convenient for a future clinical application of MSC-Exos in IBD. To understand the molecular basis mediating the anticolitic benefit of MSC-Exos, we performed proteomic analysis using iTRAQ technology to detect the protein expression profiles in MSC-Exos and the corresponding supernatants from their parent cell MSCs. Proteomic analysis revealed that MSC-Exos were enriched in proteins involved in regulating multiple biological processes associated with the anti-colitic benefit of MSC-Exos. Particularly, metallothionein-2 in MSC-Exos was required for the suppression of inflammatory responses in macrophages. Taken together, MSC-Exos are critical regulators of inflammatory responses and may be promising candidates for IBD treatment.
Project description:In order to investigate the molecular mechanisms underlying the further enhancement of Atorvastatin pretreated MSC-derived exosomes (MSCATV-Exo) in cardiac protection, we performed lncRNA sequencing on exosomes secreted from ATV pretreated MSCs and non treated MSCs to identify differentially expressed lncRNA. We found that 450 lncRNAs were identified to be upregulated and 1332 lncRNAs downregulated (over 1.5 fold change) in MSCATV-Exo compared to MSC-Exo.
Project description:In order to investigate the specific mechanisms underlying the cardioprotective effects of Tongxinluo pretreated MSC-derived exosomes (MSCTXL-Exo) in cardiac repair, we performed microRNA sequencing on exosomes secreted from Tongxinluo pretreated MSCs and non-treated MSCs to identify differentially expressed miRNA. We found that 18 miRNAs were identified to be upregulated and 25 miRNAs downregulated (over 2-fold change) in MSCTXL-Exo compared to MSC-Exo.
Project description:To explore the potential exosomal miRNAs regulating macrophage M1 polarization, we isolated and characterized inf-Exos or un-Exos, ad the miRNA profiling between inf-Exos and un-Exos was then compared by using miRNA-seq. We then performed miRNAs expression profiling analysis using data obtained from RNA-seq of inf-Exos (n = 5) and un-Exos (n = 5)