Tissue Engineering and Regenerative Medicine

Aberrant systemic artery supply results in recurrent infections in the abnormal lung lobe of intralobar pulmonarysequestration (ILS). Because of inefficient control of such symptom in clinic, surgical resection becomes the treatment of choice. In present study, we observed abnormalities associated with epithelial barriers in ILS specimen including hypersecretion of mucin and reduced expression of surfactant protein C (SPC). Compared to healthy control specimen, keratin 5-positive stem cells were less proliferative in distal airways. SPC-positive alveolar type 2 (AT2) stem/progenitor cells were also less proliferative and less in number. Transcriptional profiling analysis suggests that human aortic endothelial cells differed from human pulmonary artery endothelial cells in signal pathways associated with cell division. Array validation indicates that thrombospondin-1 (TSP1) expression was decreased in vascular cells near lesion part but increased in lesion part of ILS lobe. In vitro culture demonstrates that TSP1 exhibited an inhibitory role in mouse AT2 cell differentiation. The inhibitory effect was abolished when CD36 was knocked out in AT2 cells. These data demonstrate that distal lung stem/progenitor cells are impaired in ILS lobe and imply that restoring epithelial integrity can be beneficial for the future treatments of recurrent infections in lung pathologies.