Abstract
Background: Our understanding of mesenchymal cell subsets and their function in human lung affected by aging and in certain disease settings remain poorly described. Methods: We use a combination of polychromatic flow cytometry, prospective cell-sorting strategies, confocal imaging, and modeling of microvessel formation using advanced microfluidic chip technology to characterize mesenchymal cell subtypes in human postnatal and adult lung. Tissue was obtained from patients undergoing elective surgery for congenital pulmonary airway malformations (CPAM) and other airway abnormalities including chronic obstructive pulmonary disease (COPD). Results: Using polychromatic flow cytometry, there was a 5-fold higher fraction of EpCAM-CD45-CD31-CD14- (mesenchymal) compared with EpCAM+CD45-CD31-CD14- cells (epithelial) in unaffected postnatal human lung. The mesenchymal fraction was composed primarily of single CD90+ and CD90+CD73+ cells both enriched in niche factors CXCL12 and PDGFRα. Immunofluorescence confirmed CD90+ cells in close proximity to EpCAM+ cells some co-staining for pro-SPC in the alveolar region suggestive of an alveolar unit. Contained within the CD90+ population, a subset co-expressed the pericyte marker CD146 with immunomodulatory properties able to internalize influenza virosomes, as well as live influenza virus. Postnatal CD90+CD146+ mesenchymal cells supported microvessel formation, whereas CD90+CD146+ mesenchymal cells from COPD patients failed to do so. In congenital lung lesions, cystic airspaces and dysplastic alveolar regions were marked with an expanded underlying thick interstitium of CD90+ and CD90+PDGFRα+ cells. Conclusion: These data provide important new information regarding the immunophenotypic identity of key mesenchymal lineages and track their change in diverse setting of congenital lung lesions and other airway abnormalities including COPD.
Wang, Limei