Neoalveolarization contributes to compensatory lung growth following pneumonectomy in mice

Regeneration of gas exchange area by induction of neoalveolarization would greatly improve therapeutic options in destructive pulmonary diseases. Unilateral pneumonectomy is an established model to remove defined portions of gas exchange area and study mechanisms of compensatory lung growth. We addressed the question whether new alveoli are added to the residual lung after pneumonectomy in mice. Left-sided pneumonectomy was performed in adult C57BL/6 mice (n=11). Alveolar numbers were analyzed in lungs fixed at day 6 and 20 after pneumonectomy and in age-matched controls (n=10) using design-based stereology based on a physical fractionator. Post-fixation lung volume was determined by fluid displacement. Complete restoration of lung volume was observed 20 days after pneumonectomy. Alveolar numbers were significantly increased by 33% in residual right lungs at day 20 in comparison with control right lungs. In control left lungs, an average of 471±162 x 103 alveoli was estimated, 49% of which were regenerated by residual lungs at day 20. 74% of newly formed alveoli seen at day 20 were already present at day 6. Our data demonstrate that, in addition to growth of existing alveoli in size, neoalveolarization contributes to restoration of gas exchange area in adult mice and is induced early after pneumonectomy. Number of words in the abstract: 200