Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA300621 | ENA |
REPOSITORIES: ENA
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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: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: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:Human Induced Pluripotent Stem Cells Recapitulate Breast Cancer Patients’ Predilection to Doxorubicin-Induced Cardiotoxicity
| PRJNA306880 | ENA
Project description:Human amniotic fluid cells (AFCs) are immune-privileged with low immunogenicity and anti-inflammatory properties. Furthermore, they are high proliferative and have a broad differentiation potential, making them amenable for cell replacement therapies. Amniotic fluid (AF) is routinely obtained via amniocentesis. It contains heterogeneous populations of foetal-derived differentiated and undifferentiated progenitor cells including mesenchymal stem cells (MSCs). AF-derived mesenchymal stem cells (AF-MSCs) can self-renew and have a high proliferation and differentiation potential. In this study, we isolated AFCs from AF obtained during Caesarean sections (C-sections) and characterized them. The AFCs showed typical MSCs characteristics in relation to morphology, in vitro differentiation potential, cell surface marker expression and secreted factors. Subpopulations of AF-MSCs expressed several pluripotency-associated markers such as stage specific embryonic antigen 4 (SSEA4), c-Kit, TRA-1-60 and TRA-1-81, making them reprogrammable to induced pluripotent stem cells (iPSCs) without the use of ectopic gene expression. Additionally, they express the mesenchymal marker - Vimentin and multipotency-associated stem cell marker - CD133. Furthermore, the transcriptome and secretome analyses showed significant overlap with bone marrow-derived MSCs. C-section-derived AFMSCs can be routinely obtained without any risk to the foetus. Patient-specific AF-MSCs can be used for personalized cell therapies and disease modelling.
2018-01-12 | GSE100448 | GEO
Project description:Induced pluripotent stem cells (iPSCs) with potential for therapeutic applications can be derived from somatic cells via ectopic expression of a set of limited and defined transcription factors. However, due to risks of random integration of the reprogramming transgenes into the host genome, the low efficiency of the process, and the potential risk of virally induced tumorigenicity, alternative methods have been developed to generate pluripotent cells using nonintegrating systems, albeit with limited success. Here, we show that c-KIT+ human first-trimester amniotic fluid stem cells (AFSCs) can be fully reprogrammed to pluripotency without ectopic factors, by culture on Matrigel in human embryonic stem cell (hESC) medium supplemented with the histone deacetylase inhibitor (HDACi) valproic acid (VPA). The cells share 82% transcriptome identity with hESCs and are capable of forming embryoid bodies (EBs) in vitro and teratomas in vivo. After long-term expansion, they maintain genetic stability, protein level expression of key pluripotency factors, high cell-division kinetics, telomerase activity, repression of X-inactivation, and capacity to differentiate into lineages of the three germ layers, such as definitive endoderm, hepatocytes, bone, fat, cartilage, neurons, and oligodendrocytes. We conclude that AFSC can be utilized for cell banking of patient-specific pluripotent cells for potential applications in allogeneic cellular replacement therapies, pharmaceutical screening, and disease modeling. Total RNA obtained from mid gestation human amniotic fluid cells (AFSCs/2nd trimester AFSCs), early gestation human amniotic fluid cells (eAFSCs/1st trimester AFSCs) and human embryonic stem cells (hESCs) as described in the corresponding Materials and Methods sections.
2012-07-23 | E-GEOD-26940 | biostudies-arrayexpress
Project description:Comprehensive profiling of the secretome formulations of fetal and perinatal human amniotic fluid stem cells
| PRJNA706362 | ENA