Lung transplantation-induced cold ischemia–reperfusion injury in the murine lung
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA924286 | ENA |
REPOSITORIES: ENA
Similar Datasets
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 (IR) is an unavoidable step of organ transplantation. IR-induced injury constrains the number of donor lungs used for transplant. Here we performed longitudinal single-cell RNA sequencing (scRNA-seq) from human lungs of six individuals who underwent lung transplantation. Lung biopsies were collected after cold preservation and 2-hour reperfusion for each individual resulting in the profiling of 108,613 cells in total.
2024-10-12 | GSE220797 | 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:Our understanding on mechanisms of ischemia-reperfusion induced lung injury during lung preservation and transplantation is based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these mechanisms at transcriptomics levels, especially by focusing on the differences between human lung endothelial and epithelial cells, which are crucial for maintaining essential lung structure and function. Human pulmonary microvascular endothelial cells and human lung epithelial cells were cultured to confluent, subjected to different cold ischemic time (CIT) to mimic static cold storage with preservation solution, and then subjected to warm reperfusion with serum containing culture medium to similar lung transplantation. Cell morphology, viability and transcriptomic profiles were studied. Ischemia-reperfusion induced a CIT time-dependent cell death, which was associated with dramatic changes in gene expression. Under normal control conditions, endothelial cells showed gene clusters enriched in vascular process and inflammation, while epithelial cells showed gene clusters enriched in protein biosynthesis and metabolism. CIT 6 h alone or after reperfusion had little effects on these phenotypic characteristics. After CIT 18 h, protein biosynthesis related gene clusters disappeared in epithelial cells; after reperfusion, metabolism-related gene cluster in epithelial cells and multiple gene clusters in the endothelial cells also disappeared. Human pulmonary endothelial and epithelial cells have distinct phenotypic transcriptomic signatures. Severe cellular injury reduces these gene expression signatures in a cell type dependent manner. Therapeutics that preserve these transcriptomic signatures may represent new treatment to prevent acute lung injury during lung transplantation.
2021-04-17 | GSE172222 | GEO
Project description:Lung ischemia–reperfusion (IR) injury increases the mortality and morbidity of patients undergoing lung transplantation. The objective of this study was to determine the key initiator of lung IR injury and to evaluate pharmacological therapeutic approaches using a functional inhibitor against the identified molecule. In a mouse hilar clamp model, the combination of RNA sequencing revealed that neutrophils-derived S100A8/A9 plays a central role in inflammatory reactions in lung IR injury.
2022-11-24 | GSE203238 | GEO
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:BACKGROUND: Hypovolemia is common in lung donors before or after brain death. However, its impact on primary graft function (PGD) remains obscure. METHODS: A clinically relevant two-hit model of PGD was established by integrating hypovolemic shock (HS) and cold ischemia-reperfusion in a mouse model of orthotopic lung transplantation (LTx) from C57BL/6 to Balb/c. At -48 hours, HS was induced to donor by withdrawal of blood from femoral artery and keeping the mean arterial pressure at 15±5 mmHg for 4 h. At -24 hours, donor lungs were retrieved from mice with or without HS and stored at 0ºC until transplantation. CD11b-DTR mice were used as donor and treated with Diphtheria Toxin (DT) to deplete graft-infiltrating macrophages. RESULTS: HS mainly caused macrophage-predominant infiltration around pulmonary artery injury systemic inflammatory response, but little impairment of lung function even if in combination with cold ischemia-reperfusion. Transcriptional profiling showed HS pretreatment increased pulmonary damage and alveolar remodeling but ameliorated inflammatory infiltration when compared to one-hit model of 12 hours cold ischemia-reperfusion injury. The allografts with donor DT-treatment one day ahead of HS showed injury and dysfunction at donation and worsened further at 24 hours reperfusion, whereas the allografts with recipient DT-treatment immediately after transplantation showed similar function and histology to the control treated with saline. CONCLUSION: Donor hypovolemia causes pulmonary artery injury and infiltration but has little impact on allograft function, even in combination with 24 h cold ischemia. Graft-infiltrating macrophages are critical in protecting graft from HS-induced injury and cold ischemia-reperfusion injury.
2022-03-30 | GSE156322 | GEO
Project description:Lung ischemia-reperfusion (I/R) injury remains one of the common complications after various cardiopulmonary surgeries. I-R injury represents one potentially maladaptive response of the innate immune system which is featured by an exacerbated sterile inflammatory response triggered by tissue damage. Thus, understanding the key components and processes involved in sterile inflammation during lung I-R injury is critical to alter care and extend survival for patients with acute lung injury. We constructed a minipig surgical model of transient unilateral left pulmonary artery occlusion without bronchial involvement to create ventilated lung I-R injury. Lung tissues from minipig with sham operation (one sample), left side lung tissues (the operated side)(one sample) and right side lung tissues (the non-operated side)(one sample) from minipig with lung ischemia-reperfusion were submitted for gene expression array analysis.
2015-12-07 | E-GEOD-75560 | biostudies-arrayexpress
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
2009-01-20 | GSE14373 | GEO
Project description:Mapping Ischemia Reperfusion Inflammatory Responses in Human Lung Transplantation at Single-Cell Resolution
| PRJNA911408 | ENA