De Novo Design and Development of a Nutrient-Rich Perfusate for Ex Vivo Lung Perfusion with Cell Culture Models

Ex vivo lung perfusion (EVLP) has increased donor lung utilization through assessment of marginal lungs prior to transplantation. To develop it as a donor lung reconditioning platform, prolonged EVLP is necessary, and new perfusates are required to provide sufficient nutritional support. Human pulmonary microvascular endothelial cells and epithelial cells were used to test different formulas for basic cellular function. A selected formula was further tested on an EVLP cell culture model, and cell confluence, apoptosis, and GSH and HSP70 levels were measured. When a cell culture medium (DMEM) was mixed with a current EVLP perfusate-Steen solution, DMEM enhanced cell confluence and migration and reduced apoptosis in a dose-dependent manner. A new EVLP perfusate was designed and tested based on DMEM. The final formula contains 5 g/L Dextran-40 and 7% albumin and is named as D05D7A solution. It inhibited cold static storage and warm reperfusion-induced cell apoptosis, improved cell confluence, and enhanced GSH and HSP70 levels in human lung cells compared to Steen solution. DMEM-based nutrient-rich EVLP perfusate could be a promising formula to prolong EVLP and support donor lung repair, reconditioning and further improve donor lung quality and quantity for transplantation with better clinical outcome.

Automated summary

Ex vivo lung perfusion (EVLP) has improved lung transplant success by evaluating marginal lungs before transplantation. To develop EVLP as a platform for donor lung reconditioning, a prolonged EVLP and new perfusates providing sufficient nutritional support are necessary. A combination of DMEM and a current EVLP perfusate (Steen solution) enhanced cell function and reduced apoptosis. A new EVLP perfusate, D05D7A solution, based on DMEM was designed and tested, showing improved cell function and higher levels of GSH and HSP70 compared to Steen solution. DMEM-based nutrient-rich perfusate could prolong EVLP and improve donor lung quality for transplantation.