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Expression of Human Lung Biopsies Before and at 6 hours of EVLP

ABSTRACT: Ex vivo lung perfusion restores normothermia, ventilation and circulation to donor lungs, typically after a period of cold ischemia. This allows donor lungs to be evaluated prior to transplantation. We used microarrays to study the biological response of human lungs to Ex Vivo Lung Perfusion. These are a subset of samples previously described in the paper: Yeung, Jonathan C., et al. Towards donor lung recovery—gene expression changes during ex vivo lung perfusion of human lungs. American Journal of Transplantation 18.6 (2018): 1518-1526.

ORGANISM(S): Homo sapiens

PROVIDER: GSE127057 | GEO | 2023/09/18

REPOSITORIES: GEO

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Expression of Human Lung Before and After Ex Vivo Lung Perfusion

Project description:Ex vivo lung perfusion restores normothermia, ventilation and circulation to donor lungs, typically after a period of cold ischemia. This allows donor lungs to be evaluated prior to transplantation. We used microarrays to study the biological response of human lungs to Ex Vivo Lung Perfusion. Samples were collected from donor lungs at Toronto General Hospital. Lungs were donation after brain death (DBD)

2020-06-22 | GSE127055 | GEO

Proteomic changes to immune and inflammatory processes underlie lung preservation using ex vivo cytokine adsorption

Project description:The field of graft preservation has made considerable strides in recent years improving outcomes related to solid organ restoration and regeneration. In lungs, the use of ex vivo lung perfusion (EVLP) in line with devices and treatments has shown promising results within preclinical and clinical studies with the potential to improve graft quality. The benefit of the therapy would be to render marginal and declined donor lungs suitable for transplantation, ultimately increasing the donor pool available for transplantation. Additionally, such therapies used in machine perfusion could also increase preservation time, facilitating logistical planning. Cytokine adsorption has been demonstrated as a potentially safe and effective therapy when applied to the EVLP circuit and post transplantation. The mechanism by which this treatment improves the donor lung on a molecular basis is not yet fully elucidated. We hypothesized that there were characteristic inflammatory and immunomodulatory differences between lungs treated with and without cytokine adsorption, reflecting in proteomic changes in gene ontology pathways and across inflammation-related proteins. In the current study we investigate the molecular mechanisms and signaling pathways of how cytokine adsorption impacts the lung function when used during EVLP and when used post transplantation as hemoperfusion in a porcine model. Lung tissue from EVLP and post lung transplantation were analyzed for their proteomic profile using mass spectrometry. The inflammatory and immune processes were compared between the treated and the non-treated groups to show the differences occurring between the forms of graft preservation.

2023-10-24 | PXD044413 | Pride

Ex vivo lung perfusion enhances donor lung preservation in mice via Hippo signaling activation

Project description:Background: Ex vivo lung perfusion (EVLP) is a promising technique that allows organ preservation and repair, increasing the number of marginal donor lungs for lung transplantation. This study aimed to establish an EVLP model in mice, and to unveil the molecular mechanisms responsible of EVLP beneficial effects. Methods: The mouse EVLP system was established, and mouse lungs were exposed to: (1) without ischemia or EVLP (control), (2) 45 min EVLP followed by 135 min cold ischemia (EVLP-CI), (3) 135 min cold ischemia followed by 45 min EVLP (CI-EVLP), and (4) 180 min cold ischemia (CI). At the end of the 3-hour lung preservation period, lungs were collected for proteomic profiling.

2025-07-16 | PXD066193 |

Newly synthesized glycoproteins during ex vivo lung perfusion

Project description:Proteins that were newly-synthesized during ex vivo lung perfusion were labeled with an azido-sugar Ac4GalNAz in the perfusate. These proteins were enriched using click chemistry to attach an alkyne-desthiobiotin group to the azido-labeled proteins, then pulled out of solution using streptavidin beads. The overall goal is to better understand the effects of warm ischemia injury in lungs destined for lung transplantation.

2022-10-07 | MSV000090491 | MassIVE

Deciphering the initial steps of SARS-CoV2 infection in whole human lungs identifies macrophages as primary targets and reveals subset-specific responses.

Project description:Several in vitro models have been established to mimic the initial interaction between lung cell types and SARS-CoV-2, mainly using explant-based techniques that generated contrasted results about the cell types that were infected. These contrasting results could be due to biases in the various tissue-culture conditions. Furthermore, all these systems do not respect the spatial tissue architecture and the anatomic constraints that shape cell type interactions with viruses. In this study, we used whole human lungs maintained alive ex vivo for 10 h, based on a technique used in lung transplantation (ex vivo lung perfusion or EVLP), to analyze the first steps of SARS-CoV-2 infection in the lung. Five human donor lungs declined for transplantation were perfused and ventilated at 37°C and three of them were infected with SARS-CoV-2 using nebulization of the Wuhan lineage and D614G variants. Single-cell RNA-sequencing (scRNA-seq) using 10x Genomics 3' (v3 Chemistry) has been performed on these samples.

2024-07-04 | GSE246128 | GEO

Cell type- and time-dependent biological responses in ex vivo perfused lung grafts

Project description:Ex vivo lung perfusion (EVLP) is a largely employed technique in transplantation that permits the reassessment of marginal lungs, thereby increasing the graft pool. However its biological effects on the different lung cell types are not known. In order to advance our mechanistic understanding and further improve EVLP, we conducted a pioneer study involving single-cell RNA-seq (scRNA-seq) on two human lungs declined for transplantation. We integrated data sets generated at 4 h (clinical duration) and 10 h (prolonged duration) and revealed functional changes common to both lungs that include inflammation in most cell types, loss of barrier function in epithelial and endothelial cells especially at 10 h, and reduction of migration properties in immune cells. In addition to providing insights into the biological effects of EVLP, scRNA-seq applied to EVLP offers a highly powerful way to evaluate novel EVLP therapeutic advances that will benefit to lung transplantation.

2023-06-20 | GSE218788 | GEO

Potential Therapeutic Targets for Donor Lung Repair During Human Ex Vivo Lung Perfusion Prior to Transplantation

Project description:Potential Therapeutic Targets for Donor Lung Repair During Human Ex Vivo Lung Perfusion Prior to Transplantation

| PRJNA524402 | ENA

Human ex vivo Lung Perfusion: A Pre-Clinical Model for Lung Disease

Project description:We report the first use of ex vivo lung perfusion (EVLP) in the genetic and physiologic modification of lungs from deceased pulmonary arterial hypertension (PAH) patients and propose this as a translational platform to both (1) derive clinically relevant mechanistic insights into pulmonary pathophysiology and (2) to test treatments on human lungs. The EVLP consist in the perfusion of the lungs out of the body during 6 hours. It is a well established protocol in where basically lungs are on a table connected to a close circuit containing a special perfusion solution that is circulated through the pulmonary vein and artery using a pump. The circuit contains also a deoxygenator. The perfusion temperature and flow are adjusted gradually and after 20 mins of perfusion the ventilation is initiated. Every hour lungs are recruited in order to assess pulmonary function and collect perfusate samples. In addition to perfusate, tissue samples from the lower lobe of the left lung and bronchial alveolar lavage (BAL) are collected at times T0, 3 and 6 hr.

2015-06-02 | GSE69416 | GEO

Unraveling molecular and functional responses across three lung injury models to expand the donor lung pool

Project description:Background: Lung transplantation remains hampered by a scarcity of viable donor lungs, partially attributed to donor lung injuries. Methods: Three porcine lung injury models were studied: infection-induced using lipopolysaccharide (LPS) (n=7), aspiration-induced using endotracheal gastric content (n=7), and injury using lavage and harmful ventilation (VILI) (n=7). Molecular and functional changes from before and after the establishment of lung injury were examined with histopathology, immunohistochemistry, cytokine levels, hemodynamics, and mass spectrometric analysis of lung tissue. The respiratory tract lining fluid was analyzed using exhaled breath particles. Results: T-cell proliferation and suppression of complement activation were unique to the gastric injury, while the VILI group displayed a unique activation of monocyte chemotaxis. The LPS injury exhibited an activation of stress response proteins. Alterations in the extracellular matrix, particularly the degradation of collagen type IV and increased elastin expression were identified as a consistent indicator of acute lung injury. Additionally, increases in exhaled particles and differential expression of proteins in the RTLF correlated with deteriorating lung function. Conclusions: Molecular analysis of the lung indicated distinct key differences and similarities of donor lung injury phenotypes. Analysis of various donor lung injuries suggests a heightened emphasis on the ECM for the restoration and rejuvenation of damaged donor lungs.

2025-06-30 | PXD054562 | Pride

Expression of Human Lung by Donor Type and EVLP Type

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

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