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: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: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)
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: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:Skeletal muscle maintains remarkable regenerative ability after injury, which mainly depends on the coordination and dynamic regulation between muscle stem cells and various other cell types. Recent studies have shown that fibro/adipogenic progenitors (FAP) play an important role in skeletal muscle regeneration by coordinating the interaction between muscle stem cells and macrophages. At present, the mechanism of whether FAP cells can regulate macrophages to affect skeletal muscle regeneration remains unclear. By isolation of mouse skeletal muscle FAP cells damaged by CTX for 10 days and gathered exosomes from them called FAPD10-exos, and using the exosomes to induce macrophages in vitro, we found that they expressed high levels of M2-type factors.In summary, we believe that FAPD10-exos can promote the polarization of macrophages towards M2 phenotype by secreting exosomes, and participate in and promote the regulation and regulation of skeletal muscle regeneration to enter the stage of damage repair in the early stage of regeneration.
Project description:We hypothesized that miRNAs in the bone maroow mesenchymal stem cells (BM-MSC)-derived exosomes contributed to the phenotype change of breast cancer cells through exosome transfer. We analyzed the miRNA expression signature in BM-MSC-derived exosomes. We compared the miRNA expression levels in exosomes between BM-MSCs and adult fibroblasts (as a control). In this study, miRNA expression including in bone-marrow mesenchymal cell (BM-MSC)-derived exosomes was examined, and compared with that of exosomes derived from adult fibroblast cells or the BM-MSC cells. In addition, miRNA expression of BM-MSC exosomes was also compared with that of breast cancer cells with or without cancer stem cell marker.