Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA300621 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The anthracycline, doxorubicin (Dox), is widely used in oncology, but it may it may cause a cardiomyopathy which has dismal prognosis and cannot be effectively prevented. The secretome of multipotent human amniotic fluid-derived stem cells (hAFS) has previously been demonstrated to reduce ischemic cardiac damage. Here, it is shown that the hAFS conditioned medium (hAFS-CM) antagonizes senescence and apoptosis of cardiomyocytes and cardiac progenitor cells, two major features of Dox cardiotoxicity. Mechanistic studies with primary mouse neonatal cardiomyocytes reveal that hAFS-CM inhibition of Dox-elicited senescence and apoptosis is paralleled by decreased DNA damage and is associated with nuclear translocation of NF-kB and upregulation of a set of genes controlled by NF-kB, namely Il6 and Cxcl1, which promote cardiomyocyte survival, and Cyp1b1 and Abcb1, which encode for proteins involved in Dox metabolism and efflux, respectively. The PI3K/Akt signaling cascade, upstream of NF-kB, is potently activated by the hAFS-CM and pre-treatment with a PI3K inhibitor abrogates NF-kB accumulation into the nucleus, modulation of its target genes, and prevention of Dox-initiated senescence and apoptosis in response to the hAFS-CM. This work may lay the ground for the development of a stem cell-based paracrine therapy of chemotherapy-related cardiotoxicity.
2016-10-30 | GSE74513 | GEO
Project description:secretome proteomics analysis of human umbilical cord mesenchymal stem cells and human amniotic epithelial stem cells
2023-07-18 | PXD043861 |
Project description:Cardiomyocytes derived from human pluripotent stem cells were exposed to the cardiotoxic drug Doxorubicin in order to assess the utility of this cell system as a model for drug-induced cardiotoxicity. Cells are exposed to different concentrations of doxorubicin for up to 48 hours followed by a 12 days recovery period.
2017-12-19 | E-MTAB-6045 | biostudies-arrayexpress
Project description:Cardiomyocytes derived from human pluripotent stem cells were exposed to the cardiotoxic drug Doxorubicin in order to assess the utility of this cell system as a model for drug-induced cardiotoxicity. Cells are exposed to different concentrations of doxorubicin for up to 48 hours followed by a 12 days recovery period.
2017-10-28 | E-MTAB-6052 | biostudies-arrayexpress
Project description:Transcriptional analysis of doxorubicin-induced cardiotoxicity
| PRJNA92643 | ENA
Project description:Doxorubicin is a wildly used effective anticancer agent. However, doxorubicin use is also related to cardiotoxic side effect in some patients. Mitochondrial damage has been shown to be one of the pathogeneses of doxorubicin-induced myocardial injury. In this study, we test the hypothesis that mitochondrial transplantation might be a therapeutic strategy to prevent and ameliorate doxorubicin-induced cardiotoxicity. We demonstrated the deleterious effects of doxorubicin on mitochondrial structure and function in cardiomyocytes both in vitro and in vivo. Mitochondrial transplantation could inhibit doxorubicin-induced cardiotoxicity by directly supplying functional mitochondria. In vitro, mitochondrial transplantation improved contractile function and respiratory capacity, reduced cellular apoptosis and oxidative stress in cardiomyocytes. Mitochondria isolated from various sources, including mouse hearts, mouse and human arterial blood, and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), all exerted similar cardioprotective effects. Mechanically, mitochondrial transplantation activates glutamine metabolism in doxorubicin-treated cardiomyocytes and blocking glutamine metabolism attenuated the cardioprotective effects of mitochondrial transplantation. Overall, our study demonstrates that mitochondria isolated from arterial blood could be used for mitochondrial transplantation, which might serve as a feasible promising therapeutic option for patients with doxorubicin-induced cardiotoxicity.
2025-03-13 | MTBLS7989 | MetaboLights
Project description:Effects of VEGF-B on doxorubicin-induced cardiotoxicity
| PRJNA321605 | ENA
Project description:Amniotic fluid stem cells (AFSCs) are of interest in regenerative medicine as a non-controversial and potentially 'abundant' source of stem cells. Progress has been made in understanding amniotic fluid stem cell biology, and amniotic fluid-derived cells have been induced to form neurons, osteoblasts, muscle cells, and others. Our study evaluates change in the genome-wide expression profile of amniotic fluid stem cells during in-vitro culture, using Affymetrix U133 Plus 2.0 microarray chips. We found that only 3.08% of gene probes were differentially expressed from early to late passage of AFSC culture. The differentially expressed genes were related to biological processes or cellular function - including transcription factors, protein kinases, and cytokines/growth factors. Other gene-sets of interest were oncogenes and tumor suppressor genes, which were a very small number of genes. We further analyzed the gene sets of interest using NIH DAVID and GSEA bioinformatics databases for gene annotations analysis. Applying false discovery rate correction, there was no significant difference in the genome-wide expression profiling between early and late passage. AFSCs maintain their genome-wide expression profile during in-vitro culture. Amniotic fluid-derived c-kit-positive cells were maintained in stem cell culture and genome-wide expression changes were studied and compared between early passage and late passage in culture.
2012-08-02 | E-GEOD-39839 | biostudies-arrayexpress
Project description:<p>Functional stem cell-derived heart models offer new avenues for preclinical, animal-free physiological assessment of drug cardiotoxicity. Yet, comprehensive molecular profiling in these models remains limited, leaving key metabolic drivers of cardiotoxicity unexplored.</p><p>Here, we leveraged an innovative platform and a topology-guided integration framework to unveil the complex dose- and time-metabolic rewiring of the central carbon metabolism caused by doxorubicin-induced cardiotoxicity (DiC) in human heart tissue. Through cross-modal integration of cardiac functionality and metabolomics in 3D engineered heart tissues, we identified 20 metabolites linked to cardiac contraction and differentially affected by doxorubicin exposure. Nine of them, including carnitine esters and UDP-glucuronic acid, were never before implicated in DiC and represent promising candidates for DiC metabolic rescue.</p><p>By yielding high-resolution insights into complex biological mechanisms, our platform and mathematical framework enable metabolic and functional assessment of cardiotoxicity in functional heart models, paving the way for innovative advances in preclinical drug development.</p>
2025-12-07 | MTBLS13225 | MetaboLights
Project description:Human Induced Pluripotent Stem Cells Recapitulate Breast Cancer Patients’ Predilection to Doxorubicin-Induced Cardiotoxicity
| PRJNA306880 | ENA