Expression of human lungs at cold ischemic time (CIT) and 1-2 hrs. after reperfusion (H)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE145989 | GEO | 2023/02/01
REPOSITORIES: GEO
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Project description:Cold ischemia-reperfusion induced injury contributes to poor lung transplant outcomes. We used transcriptome sequencing to study the biological response of mouse lungs to the cold ischemia-reperfusion process. Mouse orthotopic left LTx was performed with standard cuff techniques. Briefly, the donor lungs were recovered after being flushed with 10ml low potassium dextran (LPD) solution and inflated with 50% oxygen. Cold ischemia was induced by storing donor lungs in 20ml LPD at 4°C for 24 hours. Then, the left donor lung was cuffed and implanted into recipients within 45 minutes. After the 4-hour reperfusion, the recipient mice were sacrificed and the transplanted lungs were collected.
2023-01-20 | GSE222957 | GEO
Project description:Ischemia reperfusion induced injury contributes to poor lung transplant outcomes.Microarrays were used to study the biological response of human lungs to the ischemia reperfusion process. Samples were collected from lung transplant cases at Toronto General Hospital. Lungs were donation after brain death (DBD)
2023-09-18 | GSE127242 | GEO
Project description:Study on lung transplantation encompassing a comprehensive and detailed investigation of differences at transcription level between DBD and DCD donor lungs.
2022-03-01 | GSE128204 | GEO
Project description:We aimed to investigate the effect of increased cold ischemia time (CIT) on gene expression profiles of implantation and clinically indicated biopsies early after transplantation and the impact of basiliximab (BAS) versus rabbit antithymocyte globulin (rATG) induction therapies on clinical outcomes and intragraft molecular features A retrospective, single-centered cohort study was designed to compare the safety and efficacy of rATG versus BAS for induction in patients who received a renal transplantation from a deceased donor between January 2007 and December 2012. Recipients with CIT greater than 20 hours were included in this study. Patients were excluded if they had received a prior transplantation or dual organ transplantation. Patients were followed for 12 months post-transplantation or until patient death, graft lost or lost to follow up. Patients in the rATG group received 1.5 mg per kilogram of body weight given intravenously with the initial dose given intraoperatively. Subsequent doses were given daily through post-operative day 3, for a total dose of 4.5-6.0 mg per kilogram. Dosing was adjusted based on daily white blood cell and platelet counts. BAS (20 mg given intravenously) was administered intraoperatively and the subsequent dose on day 3 post-transplantation. All patients received maintenance immunosuppression with tacrolimus, prednisone and mycophenolate mofetil. In total. 230 patients were transplanted with a CIT > 20 hours; 174 and 56 patients received rATG and BAS induction, respectively. Gene expression profiling ws carried out on a subset (n=28) of these patients' post transplant biopsies. Of those 28 patients, 16 received rATG and 12 received BAS induction treatment.
2015-09-10 | E-GEOD-72355 | biostudies-arrayexpress
Project description:Approximately 70% of kidney grafts are obtained from deceased donors, and these grafts must be preserved in hypothermic conditions to prolong their viability until transplantation. However, prolonged cold storage (CS) of kidneys results in poor long-term outcomes after transplantation. We reported previously that CS of rat kidneys for 18 h prior to transplant impaired proteasome function, disrupted protein homeostasis, and reduced graft function. The goal of the present study was to identify the renal proteins that are dysregulated by this CS-induced injury. Isolated donor Lewis rat kidneys were subject to 18-h CS and transplanted into recipient Lewis rats (CS+Tx). Autotransplantation (ATx: transplant with 0-h CS) or Sham (right nephrectomy) surgeries served as controls. The proteome of kidney homogenates was analyzed with tandem mass-tag mass spectrometry to identify CS-induced abnormalities in kidney grafts. CS injury disrupted the renal phosphoproteome in kidney grafts and dysregulated numerous signaling pathways. Integrated analysis of global proteomes and phosphoproteomes identified 15 proteins that were significantly regulated in a CS-specific manner. In particular, proteins and pathways such as complement and coagulation cascades were upregulated, while antioxidant pathways, such as glutathione, were suppressed in CS+Tx groups compared to ATx and Sham controls. This study, for the first time, provides deeper insight into the disruption of the renal graft proteome caused by CS injury and provides a novel set of pathways and molecules that can be investigated to delineate their specific role in renal transplant outcomes, ultimately improving outcomes for patients with end-stage kidney disease.
2024-04-18 | MSV000094566 | MassIVE
Project description:Ischemia reperfusion injury (IRI)-mediated primary graft dysfunction (PGD) adversely impacts both short- and long-term outcomes after lung transplantation, a procedure which remains the only treatment option for patients suffering from end-stage respiratory failure. While B cells can regulate adaptive immune responses through antibody production, antigen presentation and secretion of cytokines, their role in lung IRI is not well understood. Here, we demonstrate by intravital imaging that B cells are rapidly recruited to injured lungs, where they extravasate into the parenchyma. Using hilar clamping and transplant models, we observe that lung-infiltrating B cells produce the monocyte chemokine CCL7 in Toll-like receptor 4 (TLR4)-TRIF-dependent fashion, a critical step contributing to classical monocyte (CM) recruitment and subsequent neutrophil extravasation, resulting in worse lung function. We find that synergistic BCR-TLR4 activation on B cells is required for the recruitment of CMs to the injured lung. Finally, we corroborate our findings in reperfused human lungs, where we observe a correlation between B cell infiltration and CM recruitment after transplantation. This study uncovers a role for B cells as critical orchestrators of lung IRI. As B cells can be depleted with currently available agents, our study provides a rationale for clinical trials investigating B cell-targeting therapies.
2024-03-20 | GSE249242 | GEO
Project description:Single cell RNA sequencing was performed on CD45+Ly6G-CD64+MerTK+ macrophages isolated from the lungs of mice 5 weeks after transplantation of 4T1-Luc mammary gland tumors. The purpose of this study was to determine the unique macrophage subsets present in the lungs of mice bearing mammary tumor metastases.
2021-08-31 | GSE164302 | GEO
Project description:Ischemia-reperfusion injury (IRI) is a major cause of morbidity and mortality following conventional lung transplantation and warm ischemia may limit success of transplanting lungs from non-heart-beating donors. We sought to determine alterations in gene expression in rat lung tissue subjected to warm ischemia in vivo followed by reperfusion. Keywords: time course
2019-04-30 | GSE9634 | GEO
Project description:During heart transplantation, storage in cold preservation solution is thought to protect the organ by slowing metabolism; by providing osmotic support; and by minimising ischaemia-reperfusion (IR) injury upon transplantation into the recipient. Despite its widespread use, our understanding of the metabolic changes prevented by cold storage and how warm ischaemia leads to damage is surprisingly poor. Here, we compared the metabolic changes during warm ischaemia (WI) and cold ischaemia (CI) in hearts from mouse, pig, and human. We identified common metabolic alterations during WI and those affected by CI, thereby elucidating mechanisms underlying the benefits of CI, and how WI causes damage. Succinate accumulation is a major feature within ischaemic hearts across species, and CI slows succinate generation, thereby reducing tissue damage upon reperfusion caused by the production of mitochondrial reactive oxygen species (ROS). Importantly, the inevitable periods of WI during organ procurement led to the accumulation of damaging levels of succinate during transplantation, despite cooling organs as rapidly as possible. This damage was ameliorated by metabolic inhibitors that prevented succinate accumulation and oxidation. Our findings suggest how WI and CI contribute to transplant outcome and indicate new therapies for improving the quality of transplanted organs.
2019-09-20 | MTBLS1085 | MetaboLights
Project description:Background: Remote Ischemic Conditioning (RIC) has been proposed as a therapeutic intervention to circumvent the Ischemia/reperfusion injury (IRI) that is inherent to organ transplantation. Using a porcine kidney transplant model, we aimed to decipher the subclinical molecular effects of a RIC regime, compared to non-RIC controls. Methods: Kidney pairs (n = 8+8) were extracted from brain dead donor pigs and transplanted in juvenile recipient pigs following a period of cold ischemia. One kidney in each pair was subjected to RIC prior to reperfusion, while the other served as non-RIC control. We designed an advanced integrative -Omics strategy combining transcriptomics, proteomics, and phosphoproteomics to deduce molecular signatures in kidney tissue that could be attributed to RIC. Results: In kidney grafts taken out 10 h after transplantation we detected minimal molecular perturbations following RIC compared to non-RIC at the transcriptome level, but more pronounced effects at the proteome level. In particular, we noted that RIC resulted in response suppression of tissue inflammatory profiles. Furthermore, an accumulation of muscle extracellular matrix assembly proteins in RIC tissues was detected at the protein level, which may result in response to muscle tissue damage and/or fibrosis. Conclusions: Our data identifies subtle molecular phenotypes in porcine kidneys subjected to RIC which could aid further optimisation of remote ischaemia protocols in renal transplantation.
2022-04-04 | PXD025273 | Pride