Gene expression signatures for rat liver grafts
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE167980 | GEO | 2021/03/02
REPOSITORIES: GEO
Similar Datasets
Project description:Normothermic machine perfusion (NMP) after static cold storage is increasingly used for preservation and assessment of human donor livers prior to transplantation. Biliary viability assessment during NMP reduces the risk of post-transplant biliary complications. However, understanding molecular changes in the biliary system during NMP remains incomplete. Here, we performed RNA-seq analysis of donor livers undergoing NMP treatment and compared livers with biliary viability scores that were acceptable for transplantation vs those that were not.
2023-11-21 | E-MTAB-13501 | biostudies-arrayexpress
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:Background and Aims: Liver transplantation is a successful treatment for patients with liver failure. However, organ shortage results in over 11% of patients loosing their chance of a transplant due to worsening of their liver disease. Ischemia/reperfusion injury (IRI) is the major cause leading to graft loss after liver transplantation. Therefore, novel methods of organ-preservation have been developed in recent years to minimize IRI. One such device is the OrganOx metra, a normothermic machine perfusion (NMP) device providing oxygen and nutrition to allow aerobic metabolism and minimizing IRI. OrganOx metra has presented with several advantages compared to conventional cold storage (CS). We aimed to confirm the impact of NMP on reducing IRI and to define the underling mechanisms. Methods: We compared 12 NMP with 27 CS-preserved livers by performing gene microarray, immunoprofiling of hepatic lymphocytes and immunochemistry staining of liver tissues for assessing necrosis, platelet deposition and neutrophil infiltration, and the status of steatosis after NMP or CS pre- and post-reperfusion. Results: Recipients receiving NMP grafts showed significantly lower peak AST levels than those receiving CS grafts. NMP altered gene-expression profiles of liver tissue from pro-inflammation to pro-healing and regeneration. NMP also reduced the number of IFN- and IL-17 producing T cells and enlarged CD4posCD25highCD127negFOXP3pos Treg pool. NMP liver tissues showed less necrosis and apoptosis in the parenchyma and fewer neutrophils and platelet infiltration compared to CS liver tissues. Conclusion: Reduced IRI in NMP recipients was the consequence of the combination of inhibiting inflammation and promoting graft regeneration.
2019-04-10 | GSE112713 | 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 initiation of donor derived dendritic cell (DC) adhesion and migration are one of the key events mediated by ischemia reperfusion injury (IRI) following solid organ transplantation. Recently we have been able to demonstrate that a single donor treatment with the synthetic metalloporphyrin cobalt protoporphyrin (CoPPIX) for heme oxygenase 1 (HO-1) induction results in the reduction of donor-derived DCs following IRI thus leading to the preservation of graft long-term function. Gene expression analysis in murine liver revealed the up-regulation of the signal transducer and activator of transcription 3 (STAT3) after CoPPIX treatment. Since it has been shown that CoPPIX is able to inhibit DC maturation, we could demonstrate that DC (-LPS) induced maturation guided by the secretion of pro-inflammatory cytokines and alloreactive T cell proliferation is dependent of STAT3 phosphorylation and independent of HO-1 activity. These observations highlight the immunomodulatory capacity of STAT3 which might be of further interest for the inhibition of immune response. Keywords: dendritic cells, heme oxygenase-1 (HO-1), STAT3, cobalt protoporphyrin
2009-12-15 | GSE8452 | GEO
Project description:The initiation of donor derived dendritic cell (DC) adhesion and migration are one of the key events mediated by ischemia reperfusion injury (IRI) following solid organ transplantation. Recently we have been able to demonstrate that a single donor treatment with the synthetic metalloporphyrin cobalt protoporphyrin (CoPPIX) for heme oxygenase 1 (HO-1) induction results in the reduction of donor-derived DCs following IRI thus leading to the preservation of graft long-term function. Gene expression analysis in murine liver revealed the up-regulation of the signal transducer and activator of transcription 3 (STAT3) after CoPPIX treatment. Since it has been shown that CoPPIX is able to inhibit DC maturation, we could demonstrate that DC (-LPS) induced maturation guided by the secretion of pro-inflammatory cytokines and alloreactive T cell proliferation is dependent of STAT3 phosphorylation and independent of HO-1 activity. These observations highlight the immunomodulatory capacity of STAT3 which might be of further interest for the inhibition of immune response. Keywords: dendritic cells, heme oxygenase-1 (HO-1), STAT3, cobalt protoporphyrin For the analysis of gene expression profiles in vivo C57BL/6 mice were treated either with 5 mg/kg CoPPIX, i.p., 50 mg/kg MC, p.o. and 500 ppm CO for 6 or 24 hrs (3 animals in each group). Untreated C57BL/6 mice were used as controls (n=9). After 6 or 24 hrs of treatment animals were sacrificed and whole livers were harvested for analysis.
2010-05-18 | E-GEOD-8452 | biostudies-arrayexpress
Project description:Normothermic ex-vivo kidney perfusion (NEVKP) has demonstrated superior outcomes for donation-after-cardiovascular death (DCD) grafts compared to static cold storage (SCS). To determine the mechanisms responsible for this, we performed an unbiased genome-wide microarray analysis. Kidneys from 30kg-Yorkshire pigs were subjected to 30min of warm ischemia followed by 8hrs of NEVKP or SCS, or no storage (NS), prior to auto-transplantation. mRNA expression was analyzed on POD3 renal biopsies.
2021-07-15 | GSE155418 | GEO
Project description:Tumor microenvironment (TME) is an active player in malignant growth and spread. Changes in the composition and structure of TME and extracellular matrix can result in either suppression or facilitation of malignant tumor growth. Carcinoma‐associated fibroblasts, bone marrow-derived multipotent mesenchymal stromal cells (BMMSCs), tumor associated macrophages and other inflammatory cells all affect the composition of TME, proliferation and survival of cancer cells, angiogenesis, invasion and metastasis. The objective of this work was to investigate the effect of the interaction between bone marrow-derived BMMSCs and human oral tongue squamous cell carcinoma (OTSCC) cells in the processes of invasion and gene expression. Co-cultures of OTSCC cancer cells and BMMSCs in 3D organotypic invasion assay were used in addition to cell culture, immunological, microarray, and RNA interference techniques. Total number of 4 samples were analyzed. 2 replicates of cultured human oral tongue squamous cell carcinoma (OTSCC) cells, and 2 replicates of OTSCC cells co-cultured with bone marrow-derived multipotent mesenchymal stromal cells
2013-12-01 | E-GEOD-44458 | biostudies-arrayexpress
Project description:Using culture conditions similar to those defined for bone marrow derived mesenchymal stromal cells (BMMSCs), peripheral blood derived mesenchymal stromal cells (PBMSCs) from green fluorescent protein (GFP) transgenic rats were isolated and expanded. Despite the highly similar profile in the putative mesenchymal characteristics including fibroblastic morphology, molecular markers such as CD90, CD44, CD106, vimentin, etc., osteogenic and adipogenic differentiation potentials, significant differential expression between PBMSCs and BMMSCs was discovered in 167 genes by Affymetrix microarray. Of the 167 sequences, were there 81 genes up-regulated and 86 genes down-regulated in the PBMSCs vs BMMSCs. The gene ontological (GO) analysis further revealed that ontology terms such as cell differentiation, development, cell communication, extracellular region, etc., were significantly enriched in these 167 genes, implying potential different biological function of PBMSCs from their counterpart BMMSCs. These genes and associated proteins may also be used as markers for defining PBMSCs from BMMSCs, and more important, may provide further direction to study this elusive cell population. Keywords: mesenchymal stromal cells (MSCs), peripheral blood (PB), bone marrow (BM), green fluorescent protein (GFP) transgenic rat, microarray
2009-04-26 | GSE11283 | GEO
Project description:Mesenchymal stem cell transplantation (MSCT) has been widely used to treat a variety of human diseases. However, the detailed mechanisms underlying its success are not fully understood. Here we show that MSCT rescues recipient bone marrow mesenchymal stem cell (BMMSC) function in Fas-deficient-MRL/lpr systemic lupus erythematosus (SLE) mice via a miR-29b/Dnmt1/Notch epigenetic cascade. Using the microRNA microarray, we found that MSCT could rescue the high level of miR-29b in the recipient BMMSCs of MRL/lpr mice.
2014-03-20 | GSE55971 | GEO