Effect of Hypoxia Preconditioning on the Regenerative Capacity of Adipose Tissue-Derived Mesenchymal Stem Cells in an Experimental Model of Atherosclerotic Renal Artery Stenosis
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ORGANISM(S): Sus scrofa
PROVIDER: GSE199641 | GEO | 2022/11/15
REPOSITORIES: GEO
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Project description:Effect of Hypoxia Preconditioning on the Regenerative Capacity of Adipose Tissue-Derived Mesenchymal Stem Cells in an Experimental Model of Atherosclerotic Renal Artery Stenosis
| PRJNA820954 | ENA
Project description:Excessive iron accumulation or deficiency have detrimental consequences across species, leading to a variety of pathologies in humans. In the nematode Caenorhabditis elegans severe iron as well as oxygen deprivation induce developmental arrest. Instead, hypoxia preconditioning protects against severe hypoxia-induced neuromuscular damage and sub-lethal levels of iron depletion extend lifespan in C. elegans. The positive health outcomes of applying hypoxia preconditioning are obvious but have low feasible application. Here, we thus assessed the potential beneficial effects of genetic and chemical interventions acting via mild iron instead of oxygen depletion. We show that limiting iron availability through frataxin silencing or the iron chelator bipyridine, similar to hypoxia preconditioning, protect against hypoxia-, age- and proteotoxicityinduced neuromuscular deficits. Mechanistically, our data suggest that the beneficial effects elicited by frataxin silencing are at least in part mediated by counteracting ferroptosis, a form of non-apoptotic cell death specifically mediated by iron-induced lipid peroxidation. These is achieved by impacting on different key players of the ferroptosis machinery and likely via novel, gpx-independent redox systems. We thus point to ferroptosis inhibition as a novel strategy to promote healthy aging.
2023-04-17 | PXD040724 | Pride
Project description:Isolated perfused rat hearts exposed to isoflurane or ischemic preconditioning, a subgroup followed by 40 minutes of ischemia and 3 hours of reperfusion. Exact protocol available from the authors. Keywords = preconditioning Keywords = anesthetics Keywords = ischemia/reperfusion Keywords: other
2004-07-30 | GSE1616 | GEO
Project description:Hypoxic-ischemic (HI) injury in the developing brain is a common cause of disability in children, and there are no effective treatments at this time. Exposure to sublethal hypoxic conditions (hypoxic preconditioning) 24 hours prior to hypoxic-ischemic insult is protective in the developing rat model. We have observed protective effects on brain histopathology and on long-term sensory-motor behavioral tasks. Changes in gene expression are thought to underlie this protective effect. By comparing gene expression in rats subjected to hypoxic preconditioning or sham conditioning at several time points from 0 to 24 hrs after preconditioning, we should gain insight into the mechanisms underlying these neuroprotective effects and may identify targets for therapeutic intervention. The aim of this study is to determine the effect of hypoxic preconditioning on global gene expression, and, in littermates, to examine the effect of hypoxic preconditioning 24 h prior to hypoxic-ischemic insult on brain histopathology. We hypothesize that changes in gene expression underlie the protective effect of hypoxic preconditioning against subsequent hypoxic-ischemic insult. Gene expression will be examined in two groups, 1) preconditioned and 2) sham controls, at 4 time points. On postnatal day 6, preconditioned animals are exposed to normothermic hypoxia for 3 hrs (8.0% oxygen, 36 degrees C), and sham animals are simultaneouosly exposed to normoxia at 36 degrees C. Animals are then returned to their dams until euthanized at 4 time points (0h, 2h, 8h, and 24h later). Five brains/group/timepoint will be used, with an equal number of males and females in each group. Brains are removed and dissected on ice. Cerebral cortex is dissected from both hemispheres and rapidly frozen on dry ice. Total RNA is isolated using the QIAGEN RNeasy Protect Maxi Kit. Littermates of these animals will be exposed to hypoxic preconditioning or sham preconditioning and subjected to hypoxic-ischemic injury 24 h later. These animals are euthanized at postnatal day 14 for histopathologic evaluation of injury.
2008-06-13 | E-GEOD-4753 | biostudies-arrayexpress
Project description:Atherosclerotic renal artery stenosis (ARAS) is associated with irreversible parenchymal renal disease and regenerative stem cell therapies may improve renal outcomes. Hypoxia preconditioning (HPC) may improve the regenerative functions of adipose tissue-derived mesenchymal stem cells (AMSC) by affecting DNA 5-hydroxymethylcytosine (5hmC) marks in angiogenic genes. Here, we investigated using a porcine ARAS model, whether growth of ARAS AMSCs in hypoxia (Hx) versus normoxia (Nx) would enhance renal tissue repair, and comprehensively analyze how HPC modifies DNA hydroxymethylation compared to untreated ARAS and healthy/normal pigs (n=5 each). ARAS pigs exhibited elevated serum cholesterol, serum creatinine and renal artery stenosis, with a concomitant decrease in renal blood flow (RBF) and increased blood pressure (BP) compared to healthy pigs. Renal artery injection of either autologous Nx or Hx AMSCs improved diastolic BP, reduced kidney tissue fibrosis, and inflammation (CD3+ T-cells) in ARAS pigs. In addition, renal medullary hypoxia significantly lowered with Nx but not Hx AMSC treatment. Mechanistically, levels of epigenetic 5hmC marks (which reflect gene activation) estimated using DNA immunoprecipitation technique were elevated in profibrotic and inflammatory genes in ARAS compared with normal AMSCs. HPC significantly reduced 5hmC levels in cholesterol biosynthesis and oxidative stress response pathways in ARAS AMSCs. Thus, autologous AMSCs improve key renovascular parameters and inflammation in ARAS pigs, with HPC mitigating pathological molecular effects on inflammatory and profibrotic genes which may play a role in augmenting regenerative capacity of AMSCs.
| S-EPMC9887092 | biostudies-literature
Project description:The innate repair and regeneration potential of skeletal tissues such as the intervertebral disc and articular cartilage is extremely limited, in part due to their avascularity and low cell density. Despite recent advances in MSC-based disc and cartilage regeneration, key challenges remain, including the sensitivity of these cells to in vivo microenvironmental stress such as low oxygen and nutrient levels. The objective of this study was to investigate whether preconditioning with hypoxia and/or transforming growth factor-beta (TGF-β) can enhance MSC survival and extracellular matrix production in a low oxygen and nutrient-limited microenvironment. Secondarily, the effects of donor variability on the response of MSCs to preconditioning was examined. MSCs from multiple bovine donors were preconditioned in monolayer in normoxia or hypoxia, with or without TGF-β. The effects of preconditioning on MSC gene expression during monolayer expansion were examined using microarrays.
2019-01-01 | GSE109567 | GEO
Project description:Hypoxia episodes and areas in tumours have been associated with metastatic dissemination and poor prognosis. Given the link between tumour tissue oxygen levels and cellular metabolic activity, we hypothesised that the metabolic profile between metastatic and non-metastatic tumours would reveal potential new biomarkers and signalling cues. We have used a previously established chick embryo model for neuroblastoma growth and metastasis, where the metastatic phenotype can be controlled by neuroblastoma cell hypoxic preconditioning (3 days at 1% O2). We measured, with fibre-optic oxygen sensors, the effects of the hypoxic preconditioning on the tumour oxygenation, within tumours formed by SK-N-AS cells on the chorioallantoic membrane (CAM) of chick embryos. We found that the difference between the metastatic and non-metastatic intratumoural oxygen levels was small (0.35% O2), with a mean below 1.5% O2 for most tumours. The metabolomic profiling, using NMR spectroscopy, of neuroblastoma cells cultured in normoxia or hypoxia for 3 days, and of the tumours formed by these cells showed that the effects of hypoxia in vitro did not compare with in vivo tumours. One notable difference was the high levels of the glycolytic end-products triggered by hypoxia in vitro, but not by hypoxia preconditioning in tumours, likely due to the very high basal levels of these metabolites in tumours compared with cells. In conclusion, we have identified high levels of ketones (3-hydroxybutyrate), lactate and phosphocholine in hypoxic preconditioned tumours, all known to fuel tumour growth, and we herein point to the poor relevance of in vitro metabolomic experiments for cancer research.
2018-08-13 | MTBLS541 | MetaboLights
Project description:Preconditioning Biochar-Fungal analyses
| PRJNA415278 | ENA
Project description:Aims. The goal of the study was to identify the possible transcriptional alterations responsible for the restoration of the second window preconditioning in the metabolic syndrome heart. Methods. LDLR-/-;ob/ob (DKO) and C57Bl6/J (WT) mice were injected with ACE-inhibitor, captopril (10 mg/kg/day) or NaCl 0.9% as controls. Preconditioning (HPC) was induced by five 6-min cycles at 6% oxygen interposed with 6 min at 21% oxygen. Non-preconditioned mice underwent a sham procedure without hypoxia. Transcriptome analysis (RNA-seq) from the whole heart RNA samples, differential gene expression with Cufdiff, pathway and network analysis with Ingenuity Pathway Analysis (IPA), qRT-PCR, and transcription factor motif enrichment analysis with i-cisTarget were performed. In separate groups, the infarct size was determined histologically after a 30-min occlusion of LAD, followed by 60-min reperfusion. Results. Preconditioning could not reduce infarct size in the untreated DKO mice (1+2%, p>.05). Preconditioning reduced infarct size to 28+2% in WT-HPC and to 23+1% in WTACE-I-HPC, both p<.05. In DKOACE-I hearts, preconditioning potential was partially restored with a reduction of infarct size by 16%. Preconditioning induced low number of differentially expressed genes (DEG) in DKO hearts (29 genes, p<.05) when compared WT and WTACE-I hearts (1634 and 2215 genes respectively, p<.05). In DKOACE-I, the number of DEG after preconditioning increased to 59, p<.05. In the three groups that could phenotypically be protected, preconditioning triggered shared pathways associated with the cell cycle quiescence, such as mTORC2 signaling, eIF2 signaling, regulation of eIF4 and p70S6K signaling, and actin cytoskeleton pathway signaling. The model-specific pathways and transcription factors differed between the groups. In the WT hearts, preconditioning enriched the pathways of mitochondrial biogenesis, oxidative phosphorylation, and anti-apoptotic signalling. In the WTACE-I hearts, preconditioning enriched the pathways of immune system signaling, metabolism, and cell cycle regulation. In the DKOACE-I hearts, pathways associated with negative inotropic effect and inhibition of myocyte growth were enriched after preconditioning. Conclusion. Our findings explain the molecular mechanism behind preconditioning in the healthy and the metabolic syndrome hearts. The phenotypically cardioprotective effect of HPC was absent in the metabolic syndrome hearts and was partially reinstated after ACE-I therapy. Transcriptional response to preconditioning differs between DKO and WT hearts and is model-specific with some degree of overlap.
2019-08-01 | GSE135198 | GEO
Project description:We performed gene expression profiling by RNA sequencing (RNA-Seq) to fully characterize the gene regulation effect induced by exposure of MSCs to two hypoxic preconditioning methods. We determined the gene expression profile of 6 populations of human MSCs isolated from bone marrow and preconditioned for 6h in 2% O2 (hypoxia) or with 40μM Vadadustat (pseudohypoxia), compared to control cells cultured in 21% O2. There were 5 populations isolated from males and 1 population isolated from a female. The mean age of the BM-MSCs donors was 50.5 years and the median was 44 years. RNA-Sequencing was performed using the Illumina platform. For each library an average of 16 - 20 million read pairs were generated. Quality control checks of the sequencing raw data was conducted with FastQC, while adapter-trimming was performed with BBDUK2. The relative expression of transcripts were quantified for each donor using the Salmon program v0.8.1. Fastq files were mapped to the Homo_sapiens.GRCh37 reference genome using HISAT2 software version 2.1.0. The tximport pipeline was used to import transcript abundance datasets for the differential gene expression analysis for three groups: Control vs. Vadadustat, Control vs. Hypoxia and Vadadustat vs. Hypoxia by DESeq2 software version 1.14.1. Our results provide insight into the transcriptomic effects of these two methods of hypoxic preconditioning of MSCs.
2021-08-04 | GSE180371 | GEO