Abstract
Lung alveolar type II (ATII) cells are specialized in the synthesis and secretion of pulmonary surfactant, a lipid-protein complex that reduces surface tension to minimize the work of breathing. Surfactant synthesis, assembly and secretion are closely regulated and its impairment is associated with severe respiratory disorders. At present, well-established ATII cell culture models are not available. In this work, Decidua-derived Mesenchymal Stem Cells (DMSCs) have been differentiated into Alveolar Type II- Like Cells (ATII-LCs), which display membranous cytoplasmic organelles resembling lamellar bodies, the organelles involved in surfactant storage and secretion by native ATII cells, and accumulate disaturated phospholipid species, a surfactant hallmark. Expression of characteristic ATII cells markers was demonstrated in ATII-LCs at gene and protein level. Mimicking the response of ATII cells to secretagogues, ATII-LCs were able to exocytose lipid-rich assemblies, which displayed highly surface active capabilities, including faster interfacial adsorption kinetics than standard native surfactant, even in the presence of inhibitory agents. ATII-LCs could constitute a highly useful ex vivo model for the study of surfactant biogenesis and the mechanisms involved in protein processing and lipid trafficking, as well as the packing and storage of surfactant complexes.
Highlights
Alveoli, the terminal functional units of the lung’s respiratory zone, consist of an endoderm-derived epithelium housing two specialized cell types, the type I and type II pneumocytes
We have previously described a population of mesenchymal stem cells (MSCs) isolated from human extraembryonic membranes termed Decidua-derived Mesenchymal Stem Cells (DMSCs) with the capacity of differentiation into alveolar type II (ATII)-like cells [30]
We extend the characterization of differentiation of DMSCs into Alveolar Type II-Like Cells (ATII-LCs) in many aspects as compared to our first report (30)
Summary
The terminal functional units of the lung’s respiratory zone, consist of an endoderm-derived epithelium housing two specialized cell types, the type I and type II pneumocytes. Type II pneumocytes, named alveolar type II (ATII) cells constitute 5% of the alveolar epithelial surface area and are involved in proliferation and transdifferentiaton into a type I phenotype in response to alveolar damage [1,2,3] Their main function is the synthesis and secretion of a surface-active material known as pulmonary surfactant [4]. Much research has been carried out to study pulmonary surfactant biogenesis and secretion by primary cultures of isolated ATII cells purified mainly from mammalian lungs. This method is laborious, expensive, animal intensive and has a low yield of cells [10]. New strategies for obtaining in vitro ATII cell cultures have to be taken into account
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