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: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:The decreasing numbers of Donation after Brain Death (DBD) donors necessitates the comprehensive evaluation of Donation after Cardiac Death Donors (DCD) as a source of pancreata. The aim of this study was to characterize pancreata and islets from DCD and DBD donors with respect to markers of cellular stress that may indicate compromised islet quality. Immunohistochemical staining of pre-isolation pancreas biopsies found increased numbers of caspase 3 positive islets in DBD, while markers of oxidative stress (nitrotyrosine, CML, and HNE) were elevated in DCD. Assessment of islet quality by standard (yield, morphology, fluorescence microscopy, and glucose stimulated insulin secretion) and novel methods (flow cytometry, HPLC quantification of ATP) did not reveal significant differences. However, the post culture loss of DCD islets was increased compared to DBD, and DCD islets showed delayed functional potency when transplanted into diabetic NOD.scid mice. Microarray analysis of cultured islets showed increased expression of multiple stress pathway related genes in DCD compared to DBD. Together these data indicate that the current standard donor management, pancreas recovery and preservation practices are insufficient to quench the oxidative stress injury suffered by DCD islets which leads to loss in culture and may complicate their use in clinical transplant. Keywords: cell type comparison
2010-02-09 | GSE14839 | GEO
Project description:Background and Aims: Liver transplantation provides an effective cure for end-stage liver disease but is hampered by a severe organ shortage. Normothermic machine perfusion (NMP) of donor livers allows dynamic preservation in addition to viability assessment prior to transplantation. Little is known about the injury and repair mechanisms induced during NMP. Therefore, we examined gene and protein expression changes in a cohort of discarded human livers during NMP, stratified by liver viability. Approach and Results: 6 human livers from donation after circulatory death (DCD) underwent 12 hours of NMP, of which 3 met viability criteria. We applied bulk transcriptomics to evaluate differences in gene expression relating to injury, repair, and regenerative responses among livers based on viability. Viable livers demonstrated robust activation of innate immunity after 3 hours of NMP followed by enrichment of pro-repair and pro-survival mechanisms. Nonviable livers demonstrated delayed and persistent enrichment of innate immune responses. Viable livers demonstrated effective induction of autophagy, the cellular repair and homeostasis pathway, compared to nonviable livers. Enrichment of pro-survival signaling was also broader in these livers. Conclusions: NMP of discarded DCD human livers results in ischemia-reperfusion injury, but importantly activates autophagy as a means of cellular repair. More pronounced activation of autophagy was seen in livers that met viability criteria for transplantation. Therapeutic targeting of the autophagy mechanism may allow rehabilitation of nonviable livers for transplantation.
2022-01-25 | GSE165568 | GEO
Project description:Liver transplantation is the only treatment option for patients with end-stage liver disease. However, a persistent disparity remains between supply and demand for donor organs suitable for transplantation, resulting in a waiting list mortality of up to 20%. This has resulted in an increasing use of high-risk grafts from suboptimal, extended criteria donors, including livers from donation after circulatory death (DCD) donors, and donors with significant comorbidities such as advanced age, diabetes mellitus and livers with high fat content. While cold storage remains sufficient for livers considered optimal for transplantation, ECD grafts are more vulnerable to cold ischemic damage, resulting in many of these grafts being rejected. As an alternative to cold storage, ex-situ normothermic machine perfusion (NMP) has become an increasingly popular method for preservation, transportation and assessment of ECD livers prior to transplantation. This allows for functional assessment of the graft and provides the opportunity to assess key processes that can be used to determine organ viability. The use of both hepatocellular and biliary viability criteria in selection of suboptimal livers from ECD donors has led to the successful transplantation of these grafts with a low incidence of post-transplant cholangiopathies. However, the mechanisms of biliary injury, and recovery thereof, following static cold storage remains poorly understood. Insight into these mechanisms may further improve preservation and selection of ECD livers. Therefore, we performed an in-depth proteomics analysis of bile samples collected from human ECD livers during NMP to identify potential mechanisms linked to biliary injury, function and regeneration over the course of the perfusion, and to assess whether biliary protein profiles can distinguish between transplantable and non-transplantable grafts.
2023-11-21 | PXD046355 | Pride
Project description:The goals of this study are to investigate whether the defects of energy metabolism and/or mitochondria occurs in Nonalcoholic fatty liver disease (NAFLD), we performed liver transcriptome analysis from livers of donors who underwent organ donation after cardiac death (DCD; 6 non-NAFLD donors, 5 NAFLD donors). In this screen, a cluster of 462 transcripts were up-regulated and 447 transcripts were down-regulated in response to NAFLD. Among these differentially expressed genes , gene sets that contribute to endoplasmic reticulum stress, intrinsic apoptosis and cytokine production were enriched in NAFLD livers, whereas lipid metabolic process were suppressed in NAFLD livers, accompanied with deficient expression of the mitochondrial matrix enzyme.
2021-02-17 | GSE160016 | 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.
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:The microRNA expression profile in donation after cardiac death (DCD) livers and its ability to identify primary non function
| PRJNA280648 | ENA