Anti-Inflammatory Effect of Mesenchymal Stem Cells Facilitates Lung Preservation

MARCOS MARTIN; BERTOLOTTI ALEJANDRO; SANTA CRUZ DIEGO; LEMUS GASTON; PACIENZA NATALIA; ROBLEDO OSCAR; YANNARELLI GUSTAVO

San Diego

Congreso; ISHLT 37th Annual Meeting and Scientific Sessions; 2017

Lung transplantation is a lifesaving therapy for people living with severe, life-threatening lung disease. The high mortality rate among patients awaiting transplantation is mainly due to the low percentage of lungs that are deemed acceptable for implantation. Thus, the current shortage of lung donors may be significantly reduced by treating marginal organs with different therapeutic strategies which facilitate both organ preservation and recovery. Here, we studied whether the anti-inflammatory effect of mesenchymal stem cell (MSCs) increases lung procurement by improving organ preservation. We developed an ex-vivo lung perfusion rat model that mimics the different stages by which donor organs must undergo before implantation. The therapeutic schema was as follow: cardiac arrest, a hot and long ischemia period (2h at RT, insult), a cold ischemia time (1.5h at 4°C, with Perfadex), alveolar recruitment, and lung reperfusion with ventilation (Steen solution, 1h at RT). The therapeutic intervention occurred after 1h of hot ischemia with human umbilical cord MSCs (1x106 cells or PBS) via the pulmonary artery. Physiologic data (pressure-volume curves, lung compliance) were acquired right after the cardiac arrest and during reperfusion. Pulmonary edema, tissue histology, redox profile and neutrophil infiltration were analyzed from lung biopsies (Basal, PBS and MSCs). Interestingly, although lung edema did not change among groups, lung compliance dropped a 38% in the MSCs group, while the PBS group showed a stronger reduction (65%, p