Transplantation of human hepatic organoids rescues liver ischemic reperfusion injury in immune-deficient mice
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ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Shusen Zheng
PROVIDER: PXD052240 | iProX | Mon May 13 00:00:00 BST 2024
REPOSITORIES: iProX
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Project description:INTRODUCTION Ischemia and reperfusion injury (IRI)-elicited tissue injury contributes to morbidity and mortality in a wide range of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest 1. Ischemia-reperfusion injury is also a major challenge during organ transplantation and cardiothoracic, vascular and general surgery 1. IRI, one of the biggest challenges for organ transplantation, continues to be a vital source of morbidity among recipients, especially in liver transplantation 2. With the enlarging shortage of available donor livers, the increased use of extended criteria donor grafts further increases IRI, adversely affecting both short-term and long-term outcomes of graft and patient survival 3. Numerous studies have investigated the benefits of pharmacological, heat shock, and ischemic preconditioning interventions aimed at decreasing liver IRI 4. However, the benefit was limited. Our center has been making great effort in conquering IRI and have developed a novel surgical technique called ischemia-free liver transplantation 5. It is an ultimate method to overcome IRI in liver transplantation, but there is still a long way to popularize it. As a result, it is still of great significance to study IRI and identify the core genes in the process and the underlying mechanism. Comprehensive bioinformatics analysis has been increasingly important as a method to study various pathological and physiological condition 6. By enrolling multiple omics or combining different types of omics, comprehensive bioinformatics analysis was able to recognize key factors that could have potentially pathogenic impact such as gene expression, protein function, and downstream pathways. With the rapid development of high-throughput sequencing technologies, several transcriptomic datasets on IRI of liver transplantation have become available in the Gene Expression Omnibus (GEO) database. Herein, we recruited 3 GEO datasets to conduct comprehensive analysis with the GEO dataset from our center. Moreover, we performed the first proteome of liver tissues to study liver IRI. Then the transcriptome and proteome were used for combined analysis to reveal key factors in liver IRI.
2022-02-23 | PXD010812 | Pride
Project description:The clear benefits of ischemic preconditioning (IPC) in reducing ischemia reperfusion injury (IRI) remain indistinct in human liver transplantation. To further understand the mechanistic aspects of IPC in human deceased donor liver transplantation (DDLT), we performed microarray analyses to determine global gene expression profiles associated with IPC administration. Donor and recipient characteristics in both groups were comparable. Clinical data from our study subset and larger trial were similar. IPC increased expression of 10 transcripts at either time point with roles in: antioxidant defenses, immunological response, lipid biosynthesis, and xenobiotic metabolism. IPC decreased the expression of 1 cell development related transcript. Conclusions: 1) IPC in DDLT increased the expression of antioxidant transcripts similar to studies in animal IPC, anesthetic, and remote IPC. 2) IPC increased expression of lipogenic transcripts, which may be relevant to the clinically observed increased IRI in our IPC group. 3) Our microarray findings support our clinical observations and are compatible with the varied outcomes of hepatic IPC studies in human liver transplantation. We conducted a nested sub-study in 12/101 subjects enrolled in a prospective randomized trial of 10 min IPC in DDLT during 2003-2006. Liver biopsies were performed at the end of cold storage and at 90 minutes after allograft reperfusion. Six biopsy pairs from both IPC and No IPC (STD) groups within a narrow donor risk index range were selected. Total RNA was extracted and hybridized with Affymetrix GeneChip Human Gene 1.0 ST Array. IPC effects were examined by comparing IPC vs. STD at both time points. Transcripts whose expression changed 2-fold with p<0.05 were considered significant.
2010-05-20 | E-GEOD-15480 | biostudies-arrayexpress
Project description:The clear benefits of ischemic preconditioning (IPC) in reducing ischemia reperfusion injury (IRI) remain indistinct in human liver transplantation. To further understand the mechanistic aspects of IPC in human deceased donor liver transplantation (DDLT), we performed microarray analyses to determine global gene expression profiles associated with IPC administration. Donor and recipient characteristics in both groups were comparable. Clinical data from our study subset and larger trial were similar. IPC increased expression of 10 transcripts at either time point with roles in: antioxidant defenses, immunological response, lipid biosynthesis, and xenobiotic metabolism. IPC decreased the expression of 1 cell development related transcript. Conclusions: 1) IPC in DDLT increased the expression of antioxidant transcripts similar to studies in animal IPC, anesthetic, and remote IPC. 2) IPC increased expression of lipogenic transcripts, which may be relevant to the clinically observed increased IRI in our IPC group. 3) Our microarray findings support our clinical observations and are compatible with the varied outcomes of hepatic IPC studies in human liver transplantation.
2009-04-01 | GSE15480 | GEO
Project description:Ischemia-reperfusion injury (IRI) remains the major reason for impaired donor graft function and increased mortality post-liver transplantation. The mechanism of IRI involves multiple pathophysiological processes and numerous types of cells. However, a systematic and comprehensive single-cell transcriptional profile of intrahepatic cells during liver transplantation is still unclear. We performed a single-cell transcriptome analysis of 14,313 cells from liver tissues collected from pre-procurement, at the end of preservation and 2 h post-reperfusion. We made detailed annotations of mononuclear phagocyte, endothelial cell, NK/T, B and plasma cell clusters, and we described the dynamic changes of the transcriptome of these clusters during IRI and the interaction between mononuclear phagocyte clusters and other cell clusters. In addition, we found that TNFAIP3 interacting protein 3 (TNIP3), specifically and highly expressed in Kupffer cell clusters post-reperfusion, may have a protective effect on IRI. In summary, our study provides the first dynamic transcriptome map of intrahepatic cell clusters during liver transplantation at single-cell resolution.
2021-04-07 | GSE171539 | GEO
Project description:To investigate the molecular mechanisms underlying ischemia-reperfusion (IR) injury in liver transplantation, RNA sequencing (RNA-seq) was performed on liver specimens obtained at various stages: before ischemia and post-reperfusion. The RNA-seq analysis aimed to profile gene expression changes in response to IR injury and identify key molecular pathways involved in liver dysfunction, with a particular focus on energy metabolism-related proteins PPARα. This approach provides a comprehensive understanding of the transcriptional alterations that occur during liver transplantation, highlighting the changes in metabolic pathways such as gluconeogenesis and fatty acid oxidation. These findings may offer insights into therapeutic strategies for mitigating IR-induced damage and enhancing liver transplantation outcomes by targeting energy metabolism pathways.
2025-01-23 | GSE283907 | GEO
Project description:To determine the circRNA expression profile in hepar tissues of 12h after brain death donor liver transplantation and matched non-brain death donor liver transplantation, we uesed circRNA microArray analysis form Arraystar to examine the expression of circRNAs and circRNAs in hepar tissues of 12h after brain death donor liver transplantation and matched non-brain death donor liver transplantation.
2020-04-10 | GSE119748 | GEO
Project description:The fallopian tubes are essential to several physiological and pathological processes from pregnancy to ovarian cancer. However, current in vitro models to study their pathophysiology were validated using two-dimensional (2D) tissue sections and measuring the organoid response to female hormone stimulation. These analyses overlook the 3D heterogeneity of the tissue and the fallopian tube mechanical function (transport of an oocyte). We developed a multi-compartment organoid model of the human fallopian tube that was meticulously tuned to reflect the compartmentalization and heterogeneity of the tissue composition. We validated the proteome, cilia-driven transport function, and architectural accuracy of this organoid through a novel platform wherein organoids are quantitatively compared to a 3D single-cell resolution reference map of a healthy, transplantation-quality human fallopian tube. This organoid model was precision-engineered using our iterative platform to resemble the cellular and extracellular proteome, biological function, and 3D microanatomy of the human fallopian tube.
2023-08-12 | MSV000092646 | MassIVE
Project description:Gene expression after liver transplantation
| PRJNA794075 | ENA
Project description:Ischemia reperfusion injury (IRI) in organ transplantation remains a significant problem with limited alternative therapeutic options. Organs that undergo significant damage during IRI, particularly those enduring long warm ischemia times, undergo significant delayed graft function (DGF) after reperfusion and tend to have greater complications long term with the onset of chronic rejection. The gas molecule carbon monoxide (CO) has emerged as an agent that can suppress IRI in rodent models of solid organ transplantation. Since the use of CO is a potential therapeutic modality in humans, we tested if CO can prevent DGF in a pig model of kidney transplantation Keywords: stress response, treatment response 18 Samples from pig kidneys, two naïve controls, two timepoints, two conditions, 4 replicates
2009-01-20 | E-GEOD-14373 | biostudies-arrayexpress
Project description:We performed DNA sequencing on the plasma of 14 liver transplantation patients to study the liver DNA in the plasma.
| EGAS00001003116 | EGA