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A3821 - A Dynamic and Morphological Analysis of Airway Epithelial Stem Cells During the Maturation of Porcine Lung
Author Block: Y. Jia1, J. Yang1, J. Shi1, J. Xue1, J. Wu1, X. Liu2; 1Ningxia Medical University, Yinchuan, China, 2General Hospital, Ningxia Medical University, Yinchuan, China.
The airway epithelium, a continuous pseudostratified population of cells lining the dichotomously branching airways, provides the barrier function that defends against inhaled gases, particulates, pathogens and other xenobiotics. In humans, the airway epithelium is comprised of four major cell types, including ciliated, goblet, columnar and basal cells. While the ciliated, secretory and columnar cells constitute the primary host defense barrier, it is the basal cells, a proliferating population of cuboidal-shaped cells, that provide the major stem/progenitor cell function from which other airway epithelial cells are derived. Human lung development and critical aspects of pulmonary epithelial differentiation is mostly studied through the utilization of animal models. Due to a lack of good experimental in vitro models, much less is known about development and stem cell biology of human lungs. Encouragingly, the anatomical and physiological similarity of porcine and human organs make porcine model particularly beneficial for translational research such as therapeutics and xenotransplantation. In this context, it is the purpose to characterize the biological similarity between human and porcine airway Epithelial Stem/Progenitor Cell (EpiSPC). Histology and cellular staining analysis were used to expound morphometric analysis in the conducting airway epithelium and screening of airway EpiSPC markers of porcine by specific antigens of epithelial cells. Additionally, in vivo lineage tracing assay of Bromodeoxyuridine (BrdU) label-retaining cells (LRC) during porcine lung maturation after birth were also investigated. The results showed that in similar to other animal species, porcine lung also remains pseudostratified mucociliary epithelium and was mainly comprised of basal, ciliated, goblet and columnar cells. Basal cells are present along the trachea to bronchioles of distal lung similar to humans. Of note, a population of K14 positive basal cells expressing CD117 (c-Kit) or CD49f (ITGA6) were potential epithelial stem cells with capacity of proliferation, clonogenicity and sphere formation. Bromodeoxyuridine (BrdU) was systematically administrated into new born piglet via i.m., and BrdU-labeled cells were accessed for lineage tracing analysis. The lineage tracing assay showed that the proportion of lineage-labeled basal cells were decreased from the proximal to distal conducting airways over the time with the lung maturation. The frequency of K14 positive LRCs in the trachea epithelia were 29.29+/-1.90 %, 5.86+/-0.34%, 0.28+/-0.08% and 0.04+/-0.04% at 0, 30, 60 and 90 days post Brdu pulse. However, only rare BrdU-LRCs were determined in airway epithelia of 3-month old pig lungs. These results suggest a similarity of porcine lung to humans in airway epithelial cell biology.