Neonatal Type II Alveolar Epithelial Cell Transplant Facilitates Lung Reparation in Piglets With Acute Lung Injury and Extracorporeal Life Support.

Objectives: Type II alveolar epithelial cells have potential for lung growth and reparation. Extracorporeal membrane oxygenation is used as life support for lung impairment resulting from acute respiratory distress syndrome. We hypothesized that intratracheal transplantation of isogeneic primary type II alveolar epithelial cells in combination with extracorporeal membrane oxygenation may facilitate lung reparation for acute lung injury (ALI). Design: A randomized, controlled experiment. Setting: An animal laboratory in a university pediatric center. Subjects: Twenty-eight 4- to 6-week young piglets, weighing 7-8 kg. Interventions: Type II alveolar epithelial cells from neonatal male piglet lungs were isolated, purified, cultured, and labeled with chemical stain PKH26. After 3-6 hours of induction of ALI by IV endotoxin and mechanical ventilation (MV), young female piglets were allocated to five groups (n = 5): ALI-MV, ALI treated with MV; ALI-EC, ALI treated with both MV and venovenous extracorporeal membrane oxygenation; ALI-EC-T, ALI-EC protocol plus intratracheal type II alveolar epithelial cell transplant; CON-MV, healthy animals treated with MV; and CON-EC-T, healthy animals treated with venovenous extracorporeal membrane oxygenation. After 24 hours, animals were weaned from treatment for recovery in the ensuing 14 days, with their lungs assessed for injury and reparation. Measurements and Main Results: Lung injury for animals in ALI-MV was moderate to severe, whereas much milder injuries in ALI-EC-T and ALI-EC were found. More PKH26-labeled type II alveolar epithelial cells were detected by fluorescence in the lungs of ALI-EC-T than in CON-EC-T as further verified by the expression of messenger RNA of sex-determining region of Y chromosome. Electromicroscopically intact type II alveolar epithelial cells and prominent lattice-like tubular myelin were also found in ALI-EC-T and CON-MV but not in ALI-EC. The hydroxyproline level in lung tissue was significantly lower in ALI-EC-T than in ALI-EC and ALI-MV, with most of the lung histopathologic and pathobiologic manifestations in favor of ALI-EC-T. Conclusions: The preliminary data suggested that type II alveolar epithelial cell transplant facilitated lung reparation for ALI in this model.