title: Human decidua-derived mesenchymal stem cells differentiate into functional alveolar type II-like cells that synthesize and secrete pulmonary surfactant complexes.
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.
authors.affiliation: Departmento de Bioquímica y Biología Molecular, Facultad de Biología, Universidad Complutense, Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cerrada
authors.affiliation: Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Paz
authors.initials: P
authors.lastname: de la Torre
authors.affiliation: Departmento de Obstetricia y Ginecología, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Grande
authors.affiliation: Department of Physiology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Haller
authors.affiliation: Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Flores
authors.affiliation: Departmento de Bioquímica y Biología Molecular, Facultad de Biología, Universidad Complutense, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pérez-Gil
mesh_terms: D056809:Alveolar Epithelial Cells / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D002454:Cell Differentiation; D003656:Decidua / Q000166:cytology*; D005089:Exocytosis; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000648:ultrastructure; D010743:Phospholipids / Q000096:biosynthesis; D011663:Pulmonary Surfactants / Q000378:metabolism*; D013997:Time Factors
chemical_list: D010743:Phospholipids; D011663:Pulmonary Surfactants