Insights into the mechanisms of alveolarization - Implications for lung regeneration and cell therapies

Although the lung has extensive regenerative capacity, some diseases affecting the distal lung result in irreversible loss of pulmonary alveoli. Hitherto, treatments are supportive and do not specifically target tissue repair. Regenerative medicine offers prospects to promote lung repair and regeneration. The neonatal lung may be particularly receptive, because of its growth potential, compared to the adult lung. Based on our current understanding of neonatal lung injury, the ideal therapeutic approach includes mitigation of inflammation and fibrosis, and induction of regenerative signals. Cell-based therapies have shown potential to prevent and reverse impaired lung development. Their mechanisms of action suggest effects on both, mitigating the pathophysiological processes and promoting lung growth. Here, we review our current understanding of normal and impaired alveolarization, provide some rationale for the use of cell-based therapies and summarize current evidence for the therapeutic potential of cell-based therapies for pulmonary regeneration in preterm infants.