Development of human fetal lung in organ culture compared with in utero ontogeny |
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Authors: | David Cossar Jeanne Bell Malcolm Lang Robert Hume |
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Institution: | (1) Centre for Research into Human Development, Departments of Obstetrics, Gynaecology and Child Health, University of Dundee, Ninewells Hospital and Medical School, DO1 9SY Dundee, Scotland;(2) Department of Pathology, University of Edinburgh, Edinburgh, Scotland;(3) Department of Child Life and Health, University of Edinburgh, Edinburgh, Scotland |
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Abstract: | Summary In utero, at around 23 wk gestation, the progenitor epithelium of distal airway differentiates into type I and type II pneumatocytes.
Human fetal lung organ cultures, as early as 12 wk gestation, have the competence to self-differentiate. Distal airway epithelial
immunoreactivity to cytokeratins CK 7,8, and 18 decreases with differentiation both in utero and in organ culture, whereas
reactivity to epithelial membrane antigen remains constant in both. As distal airways dilate, the mean percentage airspace
of fetal lungs in organ culture increases to 58%, equivalent to lung of gestation 26.0±7.3 wk. In organ culture, capillary
blood vessels, visualized by vimentin immunoreactivity, remodel and more closely approximate the epithelium but without direct
invasion. In utero, at 23 wk gestation, elastin appears as condensation around airways and forms a basis for secondary crests
which, by 29 wk gestation, evolve into alveolar septae. In organ culture, no elastin is deposited, no secondary or alveolar
crests form, and the lung retains a simple saccular structure. Differentiation of the terminal airway epithelium and mesodermal
maturational events to facilitate gas exchange, such as capillary invasion or secondary-alveolar crest formation, are almost
synchronous in human lung in utero but clearly dissociate in organ culture. |
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Keywords: | Lung development human organ culture |
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