Dataset Information

Transcriptional analysis identifies potential novel biomarkers associated with successful ex-vivo perfusion of human donor lungs.

ABSTRACT:

Background

Transplantation is an effective treatment for end-stage lung disease, but the donor organ shortage is a major problem. Ex-vivo lung perfusion (EVLP) of extended criteria organs enables functional assessment to facilitate clinical decision-making around utilization, but the molecular processes occurring during EVLP, and how they differ between more or less viable lungs, remain to be determined.

Methods

We used RNA sequencing of lung tissue to delineate changes in gene expression occurring in 10 donor lungs undergoing EVLP and compare lungs that were deemed non-transplantable (n = 4) to those deemed transplantable (n = 6) following perfusion.

Results

We found that lungs deemed unsuitable for transplantation had increased induction of innate immune pathways and lower expression of oxidative phosphorylation related genes. Furthermore, the expression of SCGB1A1, a gene encoding an anti-inflammatory secretoglobin CC10, and other club cell genes was significantly decreased in non-transplantable lungs, while CHIT-1 was increased. Using a larger validation cohort (n = 17), we confirmed that the ratio of CHIT1 and SCGB1A1 protein levels in lung perfusate have potential utility to distinguish transplantable from non-transplantable lungs (AUC .81).

Conclusions

Together, our data identify novel biomarkers that may assist with pre-transplant lung assessment, as well as pathways that may be amenable to therapeutic intervention during EVLPAQ6.

SUBMITTER: Ferdinand JR

PROVIDER: S-EPMC9285052 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Transcriptional analysis identifies potential novel biomarkers associated with successful ex-vivo perfusion of human donor lungs.

Ferdinand John Robert JR Morrison Morvern Isabel MI Andreasson Anders A Charlton Catriona C Chhatwal Alisha Kaur AK Scott William Earl WE Borthwick Lee Anthony LA Clatworthy Menna Ruth MR Fisher Andrew J AJ

Clinical transplantation 20220110 4

<h4>Background</h4>Transplantation is an effective treatment for end-stage lung disease, but the donor organ shortage is a major problem. Ex-vivo lung perfusion (EVLP) of extended criteria organs enables functional assessment to facilitate clinical decision-making around utilization, but the molecular processes occurring during EVLP, and how they differ between more or less viable lungs, remain to be determined.<h4>Methods</h4>We used RNA sequencing of lung tissue to delineate changes in gene ex ...[more]

PMID: 34954872

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Project description:ObjectivesTransient heat stress (HS) application during experimental ex vivo lung perfusion (EVLP) of warm ischaemic (WI) rat lungs produces a range of therapeutic benefits. Here, we explored whether different EVLP durations after HS application would influence its therapeutic effects.MethodsIn protocol 1, WI rat lungs were exposed to HS (41.5°C, 60-90 min EVLP), and EVLP was maintained for 3, 4.5 or 6 h (n = 5/group), followed by physiological measurements (compliance, oedema, oxygenation capacity). In protocol 2, WI rat lungs treated with (HS groups) or without HS (control groups) were maintained for 3 or 4.5 h EVLP (n = 5/group), followed by physiological evaluation and measurements (lung tissue) of heat shock proteins (HSP70, HSP27, HS90, GRP78), endogenous proteins (surfactant protein-D, CC16, platelet endothelial cell adhesion molecule-1), anti-apoptotic (Bcl2, Bcl-xL) and pro-apoptotic proteins (Bcl2-associated X protein, CCAAT/enhancer binding-protein homologous protein), antioxidant enzymes (heme-oxygenase-1, nicotinamide di-phospho-nucleotide dehydrogenase quinone-1) and nitrotyrosine (oxidative stress biomarker).ResultsIn protocol 1, physiological variables were stable after 3 and 4.5 h but deteriorated after 6 h. In protocol 2, at 3 h EVLP, HS-treated lungs differed from controls by higher expression of HSP70 and heme-oxygenase-1, and lower CC16 expression. In contrast, at 4.5 h EVLP, HS-treated lungs displayed improved physiology, higher levels of all HSPs, preserved or increased expression of surfactant protein-D, CC-16 and platelet endothelial cell adhesion molecule-1, increased antioxidant and anti-apoptotic proteins, and reduced pro-apoptotic proteins and nitrotyrosine.ConclusionsThe protective effects of HS application during EVLP of WI-damaged rat lungs strictly depend on the duration of post-HS recovery. An EVLP duration of 4.5 h appears to optimize the therapeutic potential of HS, while maintaining lungs in a stable physiological state.

Dataset Information

Transcriptional analysis identifies potential novel biomarkers associated with successful ex-vivo perfusion of human donor lungs.

Background

Methods

Results

Conclusions

Publications

Transcriptional analysis identifies potential novel biomarkers associated with successful ex-vivo perfusion of human donor lungs.

Similar Datasets

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