Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1056776 | ENA |
REPOSITORIES: ENA
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Project description:ADSCs are a new type of MSC that is typically abundant in individuals. Numerous investigations reported that adipose-derived stem cell (ADSC) transplantation could ameliorate the structure and function of injured tissues. However, their protective role in premature ovarian failure remains obscure. The aim of this study was to explore the therapeutic efficacy of ADSC transplantation for chemotherapy-induced ovarian damage and microarray analyses were used to assess gene related to ovarian function.
2013-06-11 | GSE47741 | GEO
Project description:ADSCs are a new type of MSC that is typically abundant in individuals. Numerous investigations reported that adipose-derived stem cell (ADSC) transplantation could ameliorate the structure and function of injured tissues. However, their protective role in premature ovarian failure remains obscure. The aim of this study was to explore the therapeutic efficacy of ADSC transplantation for chemotherapy-induced ovarian damage and microarray analyses were used to assess gene related to ovarian function. Total RNA of ovarians of four groups was extracted using the TRIZOL Reagent according to the manufacturer's instructions. Labeling and hybridization were performed at the CapitalBio Company, according to protocols described in the 32K mouse genome arrays user manual. The data were analyzed using LuxScan 3.0 Image analysis software (CapitalBio company).
2013-06-11 | E-GEOD-47741 | biostudies-arrayexpress
Project description:<p><strong>BACKGROUND:</strong> Ischemia/reperfusion injury (IRI) is the leading cause of acute kidney injury (AKI). The current standard of care focuses on supporting kidney function, stating the need for more efficient and targeted therapies to enhance repair. Mesenchymal Stromal Cells (MSCs) and their secretome, either as conditioned medium (CM) or extracellular vesicles (EVs), have emerged as promising options for regenerative therapy, however, their full potential in treating AKI remains unknown.</p><p><strong>METHODS:</strong> In this study, we employed an in vitro model of chemically-induced ischemia using antimycin A combined with 2-deoxy-D-glucose to induce ischemic injury in proximal tubule epithelial cells. Afterwards, we evaluated the effects of MSC secretome, CM or EVs obtained from adipose tissue, bone marrow and umbilical cord, on ameliorating the detrimental effects of ischemia. To assess the damage and treatment outcomes, we analyzed cell morphology, mitochondrial health parameters (mitochondrial activity, ATP production, mass and membrane potential) and overall cell metabolism by metabolomics.</p><p><strong>RESULTS:</strong> Our findings show that ischemic injury caused cytoskeletal changes confirmed by disruption of the F-actin network, energetic imbalance as revealed by a 50% decrease in the oxygen consumption rate, increased oxidative stress, mitochondrial dysfunction and reduced cell metabolism. Upon treatment with MSC secretome, the morphological derangements were partly restored and ATP production increased by 40-50%, with umbilical cord-derived EVs being most effective. Furthermore, MSC treatment led to phenotype restoration as indicated by an increase in cell bioenergetics, including increased levels of glycolysis intermediates, as well as an accumulation of antioxidant metabolites.</p><p><strong>CONCLUSION:</strong> Our in vitro model effectively replicated the in vivo-like morphological and molecular changes observed during ischemic injury. Additionally, treatment with MSC secretome ameliorated proximal tubule damage, highlighting its potential as a viable therapeutic option for targeting AKI.</p>
2023-10-16 | MTBLS6279 | MetaboLights
Project description:Phenotypic changes induced by extracellular vesicles (EVs) have been implicated in the recovery of acute kidney injury (AKI) induced by mesenchymal stromal cells (MSCs). miRNAs are potential candidates for cell reprogramming towards a pro-regenerative phenotype. The aim of the present study was to evaluate whether miRNA de-regulation inhibits the regenerative potential of MSCs and derived-EVs in a model of glycerol-induced AKI in SCID mice. For this purpose, we generated MSCs depleted of Drosha, a critical enzyme of miRNA maturation, to alter miRNA expression within MSCs and EVs. Drosha knock-down MSCs (MSC-Dsh) maintained the phenotype and differentiation capacity. They produced EVs that did not differ from those of wild type cells in quantity, surface molecule expression and internalization within renal tubular epithelial cells. However, EVs derived from MSC-Dsh (EV-Dsh) showed global down-regulation of miRNAs. Whereas, wild type MSCs and derived EVs were able to induce morphological and functional recovery in AKI, MSC-Dsh and EV-Dsh were ineffective. RNA sequencing analysis showed that genes deregulated in the kidney of AKI mice were restored by treatment with MSCs and EVs but not by MSC-Dsh and EV-Dsh. Gene Ontology analysis showed that down-regulated genes in AKI were associated with fatty acid metabolism. The up-regulated genes in AKI were involved in inflammation, ECM-receptor interaction and cell adhesion molecules. These alterations were reverted by treatment with wild type MSCs and EVs, but not by the Drosha counterparts. In conclusion, miRNA depletion in MSCs and EVs significantly reduced their intrinsic regenerative potential in AKI, suggesting a critical role of miRNAs. RNA-seq
2015-05-07 | E-GEOD-59958 | biostudies-arrayexpress
Project description:Chronic Pseudomas aeruginosa infection in the lung is a common in people with cystic fibrosis (CF). Current therapies for CF fail to eliminate persistent bacterial infections, chronic inflammation, or irreversible lung damage. Our group engineered mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) to carry the microRNA let-7b-5p as a dual anti-infective and anti-inflammatory treatment. In a preclinical CF mice model, we found that let-7b-5p-loaded MSC EVs reduced P. aeruginosa burden, immune cells and proinflammatory cytokines in the lungs. This research hypothesized two mechanisms of the observed effects in the mouse model: anti-inflammatory properties of the let-7b-5p-loaded MSC EVs and inhibition of antibiotic-resistant P. aeruginosa biofilm formation in CF airways. Primary human broncial epithelial cells (pHBECs) were exposed to P. aeruginosa and treated with differet MSC EV conditions. The results demonstrated that MSC EVs engineered to contain let-7b-5p effectively blocked the formation of P. aeruginosa biofilms on pHBECs while also reducing P. aeruginosa-induced inflammation by CF-pHBECs.
2025-06-16 | GSE295607 | GEO
Project description:Acute lung injury (ALI) is characterized by excessive inflammation and alveolar damage, arising from pathogens or systemic insults such as sepsis, and can progress to severe acute respiratory distress syndrome (ARDS). Current treatments, including mechanical ventilation, remain largely supportive, emphasizing the urgent need for the potent, cell-free therapeutic modalities. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as promising candidates for lung repair, but insufficient immunosuppressive capacity often limits their efficacy. Human adipose-derived mesenchymal stem cells (hADMSCs) were primed with IFN-γ and TNF-α to enhance the immunomodulatory properties of their secreted EVs. We characterized primed MSC-EVs (P-MEVs) and unprimed control MSC-EVs (C-MEVs) by transmission electron microscopy, nanoparticle tracking analysis, and western blotting for EV markers. Functional assays in THP-1 and A549 cells examined anti-inflammatory potency and barrier regeneration against lipopolysaccharide (LPS)-induced damage. A preclinical mouse model of LPS-induced ALI was used to evaluate inflammatory cytokine expression, immune cell infiltration, pulmonary edema, and vascular leakage. Finally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected Vero E6 cells were tested to explore the antiviral and anti-inflammatory potential of P-MEVs. Primed hADMSCs exhibited elevated expression of immunosuppressive molecules (e.g., COX-2, IDO, TSG-6), without changing EV morphology or yield. P-MEVs mitigated LPS-induced inflammation more effectively than C-MEVs in THP-1 and A549 cells. In vivo , P-MEVs more robustly attenuated inflammatory cytokines, immune cell recruitment, and lung injury markers in mice challenged with LPS. In SARS-CoV-2-infected Vero E6 cells, P-MEVs suppressed cytopathic effects and inflammatory responses more potently than C-MEVs. Mechanistic analyses revealed that these enhancements were associated with elevated miRNA levels, involved in inhibiting inflammatory pathways.
2025-07-22 | GSE293280 | GEO
Project description:Acetaminophen (APAP) overdose is the major cause of drug-induced liver injury (DILI) and acute liver failure (ALF), and patients with advanced APAP toxicity rarely benefit from N-acetylcysteine (NAC), which is the first-line agent used in the clinic. Mesenchymal stromal cells (MSCs) and their extracellular vesicles (MSC-EVs) have shown promising effects in the treatment of DILI by decreasing neutrophil infiltration. However, the specific mechanism underlying the therapeutic effects of MSCs or MSC-EVs still needs to be elucidated. In this study, by using RNA-seq, we found that CXCL1, which is a chemoattractant for neutrophils, is a key molecule in MSC-mediated amelioration of DILI, and by luciferase reporter assay, we verified that MSC-EV-derived miR-186-5p binds to the 3’-UTR of CXCL1 to inhibit its expression in hepatocytes. Neutralizing CXCL1 reduces APAP-induced liver damage in vivo, and the agomir miR-186-5p shows excellent potential in the treatment of DILI. Overall, these findings suggest that the use of MSC-EVs may be a promising novel strategy for preventing DILI and that targeting the miR-186-5P/CXCL1 axis is a feasible approach for improving the efficacy of MSCs in the treatment of DILI.
2024-11-13 | GSE252192 | GEO
Project description:Retinitis pigmentosa (RP) is a rod-cone degenerative disease that induces irreversible vision loss. Stem cell-derived extracellular vehicles (EVs) have been reported to prevent retinal neurons from apoptosis and inflammation, but the molecular mechanisms remained unclear. Here we probed the ability of mesenchymal stem cell-derived EVs (MSC-EVs) to protect the retinas of RP model mice rd10 and explored the underlying mechanisms. Treatment with MSC-EVs increased the survival of photoreceptors and preserved their structure and visual function. Mechanistically, MSC-EVs suppressed the activation of microglial, Müller glial, macrophages and the NF-κB pathway. MSC-EVs upregulated anti-inflammatory cytokines and downregulated pro-inflammatory cytokines. MSC-EVs application in vitro decreased the number of TUNEL-positive photoreceptor cell line 661W co-cultured with LPS-stimulated glial cell BV2, with similar impact on the cytokine expression as in vivo study. MiR-146a, one of the major miRNAs in MSC-EVs was upregulated in co-cultured cells after MSC-EVs treatment. Upregulation of miR-146a decreased the expression of the transcription factor Nr4a3, and its inhibition promoted Nr4a3 expression in both cells. Nr4a3 was further identified as the target gene of miR-146a. Therefore, MSC-EVs delays retinal degeneration in rd10 mice mainly by its anti-inflammatory effect via the miR-146a-Nr4a3 axis, indicating a strong potential of applying MSC-EVs to treat neurodegenerative diseases.
2022-04-16 | GSE200621 | GEO
Project description:Phenotypic changes induced by extracellular vesicles (EVs) have been implicated in the recovery of acute kidney injury (AKI) induced by mesenchymal stromal cells (MSCs). miRNAs are potential candidates for cell reprogramming towards a pro-regenerative phenotype. The aim of the present study was to evaluate whether miRNA de-regulation inhibits the regenerative potential of MSCs and derived-EVs in a model of glycerol-induced AKI in SCID mice. For this purpose, we generated MSCs depleted of Drosha, a critical enzyme of miRNA maturation, to alter miRNA expression within MSCs and EVs. Drosha knock-down MSCs (MSC-Dsh) maintained the phenotype and differentiation capacity. They produced EVs that did not differ from those of wild type cells in quantity, surface molecule expression and internalization within renal tubular epithelial cells. However, EVs derived from MSC-Dsh (EV-Dsh) showed global down-regulation of miRNAs. Whereas, wild type MSCs and derived EVs were able to induce morphological and functional recovery in AKI, MSC-Dsh and EV-Dsh were ineffective. RNA sequencing analysis showed that genes deregulated in the kidney of AKI mice were restored by treatment with MSCs and EVs but not by MSC-Dsh and EV-Dsh. Gene Ontology analysis showed that down-regulated genes in AKI were associated with fatty acid metabolism. The up-regulated genes in AKI were involved in inflammation, ECM-receptor interaction and cell adhesion molecules. These alterations were reverted by treatment with wild type MSCs and EVs, but not by the Drosha counterparts. In conclusion, miRNA depletion in MSCs and EVs significantly reduced their intrinsic regenerative potential in AKI, suggesting a critical role of miRNAs.
2015-05-07 | GSE59958 | GEO