The microRNA expression profile in donation after cardiac death (DCD) livers and its ability to identify primary non function
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ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE67689 | GEO | 2015/04/09
SECONDARY ACCESSION(S): PRJNA280648
REPOSITORIES: GEO
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Project description:The microRNA expression profile in donation after cardiac death (DCD) livers its ability to identify primary non function DCD livers are a marginal organ and their usein transplantation is associated with a higher risk of primary non function (PNF), or early graft dysfunction (EGD). We compared a three groups of DCD livers defined as PNF (n=7) retransplanted within a week, good functional outcome (n=7) AST < 1000IU/L and EGD (n=9) AST>2500IU/L . RNA was extracted from archived histology samples and miRNA expression was analysed using the affymetrix Genechip miRNA 2.0 assays.
2015-04-09 | E-GEOD-67689 | biostudies-arrayexpress
Project description:In DCD organ donation one of the significant problems for the organ is the inflammatory response due to ischaemiua reperfusion injury caused by warm ischaemia prior to retrieval followed by warm reoxygenation upon transplantation. We developed a model where a DCD kidney was retrieved and stoired overnight then the organ was surgically attached to the femoral artery of a recipient rat and blood flow restored for up to six hours to simulate early ischaemia reperfusion injury (IRI). The recipient rats consisted of a control group compared to groups recieveing either low molecular weight heparin or an anti-inflammatory peptide to assess their activity in ameliorating IRI. We used equimolar pooled RNA samples from each group to perform an exploratory microarray experiment.
2012-02-06 | GSE35555 | GEO
Project description:In DCD organ donation one of the significant problems for the organ is the inflammatory response due to ischaemia reperfusion injury caused by warm ischaemia prior to retrieval followed by warm reoxygenation upon transplantation. We developed a model where a DCD kidney was retrieved and preserved using hypothermic machine perfusion with cold University of Wisconsin solution with/without the addition of heparinoids low molecular weight heparin and pentosan polysulfate (PPS) followed by warm oxygenated perfusion with modified Krebs-Henseleit buffer to simulate early ischaemia reperfusion injury (IRI). The donor rats consisted of a control group cold perfusion group compared to warm perfusion and groups treated with either low molecular weight heparin or PPS to assess their activity in ameliorating IRI. We used equimolar pooled RNA samples from each group to perform an exploratory microarray experiment
2012-03-22 | GSE36671 | GEO
Project description:In DCD organ donation one of the significant problems for the organ is the inflammatory response due to ischaemiua reperfusion injury caused by warm ischaemia prior to retrieval followed by warm reoxygenation upon transplantation. We developed a model where a DCD kidney was retrieved and stoired overnight then the organ was surgically attached to the femoral artery of a recipient rat and blood flow restored for up to six hours to simulate early ischaemia reperfusion injury (IRI). The recipient rats consisted of a control group compared to groups recieveing either low molecular weight heparin or an anti-inflammatory peptide to assess their activity in ameliorating IRI. We used equimolar pooled RNA samples from each group to perform an exploratory microarray experiment. Donor kidneys were harvested and static cold stored in University of Wisconsin (UW) Solution overnight before being surgically connected to the femoral artery of a recipient rat to simulate transplantation and whole blood ischaemia reperfusion injury. The model was then used to test the anti-inflammatory properties of the glycosaminoglycan heparin and a peptide based upon the heparin binding domain of the pro-inflammatory chemokine CCL5. The treatments were delivered as a bolus in normal saline and control recipients were given normal saline as a control. The kidneys underwent perfusion by normal blood flow for a period of up to six hours after which the recipient was euthanased and the donor kidney was removed. Half of the donor kidney was used to extract RNA and half taken for immunohistochemical analysis. The RNA was extracted using the Tri reagent and stored in RNA Later. The qualitative best three RNAs from each group were quantified by fluorimetry and mixed in an equimolar manner and used for microarray analysis.
2012-02-06 | E-GEOD-35555 | biostudies-arrayexpress
Project description:In DCD organ donation one of the significant problems for the organ is the inflammatory response due to ischaemia reperfusion injury caused by warm ischaemia prior to retrieval followed by warm reoxygenation upon transplantation. We developed a model where a DCD kidney was retrieved and preserved using hypothermic machine perfusion with cold University of Wisconsin solution with/without the addition of heparinoids low molecular weight heparin and pentosan polysulfate (PPS) followed by warm oxygenated perfusion with modified Krebs-Henseleit buffer to simulate early ischaemia reperfusion injury (IRI). The donor rats consisted of a control group cold perfusion group compared to warm perfusion and groups treated with either low molecular weight heparin or PPS to assess their activity in ameliorating IRI. We used equimolar pooled RNA samples from each group to perform an exploratory microarray experiment Donor kidneys were harvested and preserved by hypothermic machine perfusion with University of Wisconsin (UW) Solution for 3 hours followed by warm oxygenated perfusion with modified Krebs-Henseleit buffer for 30 minutes to simulate transplantation and whole blood ischaemia reperfusion injury. The model was then used to test the anti-inflammatory properties of the glycosaminoglycan heparin and PPS when used as supplements into perfusate solutions. Half of the donor kidney was used to extract RNA using the Tri reagent and stored in RNA Later. The qualitative best three RNAs from each group were quantified by fluorimetry and mixed in an equimolar manner and used for microarray analysis.
2012-03-22 | E-GEOD-36671 | biostudies-arrayexpress
Project description:This study aims to investigate the protective effects and underlying mechanisms of hypothermic machine perfusion (HMP) on ischemia-reperfusion injury (IRI) in liver grafts from donation after cardiac death (DCD), with a specific focus on the regulation of KLF2 expression and its role in modulating macrophage efferocytosis.
2025-05-05 | GSE296118 | GEO
Project description:Delayed graft function (DGF) is commonly defined as dialysis in the first week post-transplant. This definition, though readily applicable, is too generic and unable to distinguish between “types� of DGF or time needed to recover function. We aimed to profile biological pathways in DCD kidney donors that correlate with DGF and discriminate different durations. N=30 DCD kidney biopsies were selected from the UK Quality in Organ Donation biobank and stratified according to DGF duration (immediate function, IF n=10; “short-DGF� (1-6 days), SDGF n=10; “long-DGF� (7-22 days), LDGF n=10). Samples were matched for donor and recipient demographics and analysed by label-free quantitative proteomics, yielding identification of N=3,378 proteins. Ingenuity Pathway Analysis on differentially abundant proteins showed that SDGF kidneys presented stress response pathways upregulation, while LDGF presented impaired response to stress, compared to IF. LDGF showed extensive metabolic deficits compared to IF and SDGF. DCD kidneys requiring dialysis only in the first week post-transplant present acute cellular injury at donation, alongside repair pathways upregulation. In contrast, DCD kidneys requiring dialysis longer beyond 7 days present minimal metabolic and antioxidant responses, suggesting current DGF definitions might not be adequate in distinguishing different types of injury in the donor kidneys contributing to DGF.
2024-05-23 | PXD038196 | Pride
Project description:Lung donation after cardiac death (DCD), in contrast to donation after brain death (DBD), is a promising and increasingly common method to help relieve the shortage of donor organs. However, the pathogenetic consequences of retrieved lungs after DCD vs. DBD have not been clarified. We aimed to study the differential gene expression profiles in lungs of DCD and DBD patients.
2009-11-12 | GSE18995 | GEO
Project description:Lung donation after cardiac death (DCD), in contrast to donation after brain death (DBD), is a promising and increasingly common method to help relieve the shortage of donor organs. However, the pathogenetic consequences of retrieved lungs after DCD vs. DBD have not been clarified. We aimed to study the differential gene expression profiles in lungs of DCD and DBD patients. DCD patients were matched with DBD lung transplant cases from a prospectively maintained database. The number of tissue samples included in this study was 6 pre- and 5 post-transplant in DCD and 12 pre- and 12 post-transplant in DBD for a total number of 35 lung tissue samples.
2009-11-11 | E-GEOD-18995 | biostudies-arrayexpress
Project description:Heart donation after circulatory death (DCD) can expand graft supply, but it exposes hearts to myocardial ischemia–reperfusion injury (IRI). Although sex differences in myocardial IRI are recognized, they remain underexplored in DCD. Therefore, we aimed to investigate whether sex differences induce changes in the expression of genes in response to cardiac DCD conditions, including IRI, which may contribute to sexual dimorphism in graft quality. Male, female, and ovariectomized (OVX) Wistar rat hearts underwent simulated DCD protocol with 0 or 22 minutes of warm ischemia, followed by oxygenated reperfusion under left-ventricular loading. Functional recovery was assessed and left-ventricular tissue analyzed by bulk RNA-sequencing. Warm ischemia reduced recovery in all sexes. Recovery of left ventricular function was significantly better in females than in males, with OVX resembling the males. Reperfusion induces inflammatory and hypoxia-responsive gene programs in all sexes. Overall, 136 genes correlated with recovery, many of which were more abundant in females, consistent with a role in improved post-ischemic function. Among these genes, Igfbp3, Fam78b, and Galnt10 were enriched in females compared to males and OVX, supporting a role for female sex hormones. Compared to male hearts, cardiac recovery is significantly higher in female hearts after exposure to DCD conditions and is accompanied by an increased expression of genes related to core homeostatic programs that have been connected to increased recovery. A significantly higher expression of genes related to energy metabolism, including fatty acid metabolism and inflammatory pathways, were more highly expressed in males compared to females and are associated with decreased recovery. This study identifies potential therapeutic targets underlying sex-specific differences in DCD heart recovery and highlights the importance of treating DCD hearts in a sexually dimorphic manner, considering differences in inflammatory pathways and metabolic adaptations, to improve cardiac graft quality in both sexes.
2026-05-26 | GSE317340 | GEO