Cutaneous burn diminishes beneficial effect of intravenously administered mesenchymal stem cells on acute lung injury induced by smoke inhalation in sheep.

Abstract

To investigate effects of intravenously administered allogeneic mesenchymal stem cells (MSCs) on burn/smoke-induced lung injury. Sheep were subjected to 40%, third-degree flame skin burn and smoke inhalation under deep anesthesia and analgesia. One-hour after injury, PlasmaLite A (control) or 200 million MSCs (treatment) were intravenously administered. Pulmonary oxygenation index, PaO₂/FiO₂ ratio, lung-lymph flow, and bloodless lung wet-to-dry weight ratio were measured. Distribution of MSCs and stromal cell-derived factor-1 (Sdf-1) protein level were determined in lung and skin tissues. Effects of burn exudate on MSCs migration were characterized. MSCs did not attenuate pulmonary dysfunction. The number of MSCs was significantly higher in lungs of sheep with smoke inhalation compared with those with burn/smoke injury. In contrast, number of MSCs was significantly higher beneath burned skin in sheep with burn/smoke than in unburned skin of sheep with smoke inhalation only. Expression of Sdf-1 protein was increased in the burned skin compared to unburned skin. Effects of burn exudate on cultured MSCs proliferation differed depending on collection time. Skin burn diminishes beneficial effects of MSCs on smoke-induced lung injury, by promoting migration of MSCs from the pulmonary tissue to the injured skin area, possibly via expression of Sdf-1 protein.