Mesenchymal Stem Cell therapy maximizes lung preservation by preventing ischemic organ injury

Abstract

Background & Aim Recently, we reported that local infusion of human umbilical cord-derived mesenchymal stem cells (MSCs) during donor lung ablation may increase lung availability by improving organ preservation. We found that MSCs protect donor lungs against ischemic injury by reducing oxidative damage and neutrophil extravasation. Pre-conditioning has emerged as a strategy to improve MSC-based therapies. Here, we studied whether the preservation capacity of MSCs may be enhanced by their pre-activation into an anti-inflammatory phenotype with TNF-alpha (TNF-a). Methods, Results & Conclusion We settled a lung preservation model in rats that mimics the different phases by which donor organs must undergo before implantation which consist on: cardiac arrest, warm ischemia (2h at room temperature), cold ischemia (1.5h at 4°C, with Perfadex), and normothermic lung perfusion with ventilation (Steen solution, 1h). After 1h of warm ischemia, 1 × 10^6 cells (MSCs, or TNF-a treated cells) or vehicle were infused via the pulmonary artery. Physiologic data (pressure-volume curves) were acquired right after the cardiac arrest and at the end of the perfusion. Lung biopsies were taken at the end of the perfusion to study edema formation, neutrophil infiltration, redox profile, etc. Interestingly, although the TNF-a treated cells showed an anti-inflammatory phenotype in vitro, we did not register a significant change in their preservation capacity. In this line, lung compliance decreased 39% and 35% in the MSCs- and TNF-a-treated groups, respectively, while the vehicle group showed a stronger reduction (72%, p These results suggest that, in this therapeutic conditions, the anti-inflammatory effect of non-activated MSCs is strong enough to conserve the functionality of the lung during ischemia, and reaffirm the notion that cell therapy is a novel tool for organ preservation.