Abstract
SummaryComplex human airway cellular organization where extracellular matrix (ECM) and epithelial and stromal lineages interact present challenges for organ study in vitro. Current in vitro lung models that focus on the lung epithelium do not represent complex airway morphology and cell-ECM interactions seen in vivo. Models including stromal populations often separate them via a semipermeable barrier precluding cell–cell interaction or the effect of ECM mechanics. We investigated the effect of stromal cells on basal epithelial cell-derived bronchosphere structure and function through a triple culture of human bronchial epithelial, lung fibroblast, and airway smooth muscle cells. Epithelial–stromal cross-talk resulted in epithelial cell-driven branching tubules with stromal cells surrounding epithelial cells termed bronchotubules. Agarose– Matrigel scaffold (Agrigel) formed a mechanically tuneable ECM, with adjustable viscoelasticity and stiffness enabling long-term tubule survival. Bronchotubule models may enable research into how epithelial–stromal cell and cell–ECM communication drive tissue patterning, repair, and development of disease.
Highlights
The airway is a complex organ consisting of highly branched tubes that provide air to the alveoli enabling gas exchange
Current in vitro lung models that focus on the lung epithelium do not represent complex airway morphology and cell-extracellular matrix (ECM) interactions seen in vivo
Models including stromal populations often separate them via a semipermeable barrier precluding cell–cell interaction or the effect of ECM mechanics
Summary
The airway is a complex organ consisting of highly branched tubes that provide air to the alveoli enabling gas exchange. These tubes contain multiple layers of interacting cells and the development, maintenance, and regeneration of the airway is governed by the cell–cell and cell–extracellular matrix (ECM) interactions. The airway is formed from a pseudostratified epithelial layer of mucous and ciliated cells underlined by basal cells attached to a basement membrane ECM (Hogan et al, 2014; Rock et al, 2010). The basement membrane separates the epithelium from the interstitial matrix (lamina propria) that contains immune and fibroblast cells as well as vasculature (Hogan et al, 2014; Rock et al, 2010). Perturbation of cell-cell and cell-ECM mechanical dynamics is associated with diseases such as interstitial pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) (Zhou et al, 2018; Burgstaller et al, 2017; Bonnans et al, 2014; Volckaert et al, 2013; Yuan et al, 2018)
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