Epithelial-stromal cell interactions and ECM mechanics drive the formation of airway-mimetic tubular morphology in lung organoids
File(s)
Published version
Author(s)
Güney, Tankut G
Herranz, Alfonso Muinelo
Mumby, Sharon
Dunlop, Iain E
Adcock, Ian M
Type
Journal Article
Abstract
Complex human airway cellular organisation where extracellular matrix (ECM), 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.
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.
Date Issued
2021-09-24
Date Acceptance
2021-08-26
Citation
iScience, 2021, 24 (9), pp.1-16
ISSN
2589-0042
Publisher
Elsevier BV
Start Page
1
End Page
16
Journal / Book Title
iScience
Volume
24
Issue
9
Copyright Statement
© 2021 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.sciencedirect.com/science/article/pii/S2589004221010294?via%3Dihub
Subjects
Bioengineering
Biomechanics
Biotechnology
Tissue Engineering
primary airway epithelial cell
matrigel
agarose
Young’s Modulus
airway smooth muscle
airway fibroblast
Publication Status
Published
Article Number
103061
Date Publish Online
2021-08-30