Due to acute lung injury (ALI), only 20% of donated lungs are suitable for transplant and of those, 25% develop primary graft dysfunction. Ex vivo lung perfusion (EVLP) may improve lung quality, but the molecular mechanisms driving this are unclear. Here, we define and validate a set of molecular markers that quantify ALI to monitor repair during EVLP.

32 peripheral swine lung biopsies were collected from EVLP (N=26), cold static perfusion (CSP, N=4) and in vivo (IV, N=2) conditions at 0 (T0) and 12 hours (T12). RNA expression of 53 genes previously associated with ALI were quantified with the NanoString nCounter system along with histological parameters in all samples. Functional parameters were documented during EVLP. Data were analyzed with nSolver and R.

Heat map analysis demonstrated differing gene set clustering between EVLP T0 and T12 (Fig 1). Based on this, we identified 14 'repair' genes most upregulated and 7 'injury' genes least upregulated at T12. 'Repair' gene expression correlated with P/F ratio (r=0.513; p=0.007) and compliance (r=0.497; p=0.010), and was inversely correlated with PVR (r=0.450; p=0.021), interstitial inflammation (r=0.395; p=0.028) and neutrophils/HPF (r=0.425; p=0.017). In contrast, 'injury' gene expression inversely correlated with compliance (r=0.440; p=0.025) and PAP (r=0.465; p=0.017) and correlated with PVR (r=0.409; p=0.038). Principal component analysis confirmed positive association of 'repair' and inverse association of 'injury' gene expression with EVLP treatment exposure (Fig 2).

We identified gene sets for ALI quantification that may be used for molecular monitoring of tissue repair during EVLP, a potential tool for tailoring ex vivo protocols in human transplant lungs.

CITATION INFORMATION: Dromparis P, Wagner S, Aboelnaz N, Luc J, Freed D, Nagendran J, Mengel M, Adam B. Expression of Injury and Repair Genes in Ex Vivo Perfused Swing Lung Transplants. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress