Branching morphogenesis of immortalized human bronchial epithelial cells in three-dimensional culture.
While mouse models have contributed in our understanding of lung development, repair and regeneration, inherent differences between the murine and human airways requires the development of new models using human airway epithelial cells. In this study, we describe a three-dimensional model system using human bronchial epithelial cells (HBECs) cultured on reconstituted basement membrane. HBECs form complex budding and branching structures on reconstituted basement membrane when co-cultured with human lung fetal fibroblasts. These structures are reminiscent of the branching epithelia during lung development. The HBECs also retain markers indicative of epithelial cell types from both the central and distal airways suggesting their multipotent potential. In addition, we illustrate how the model can be utilized to understand respiratory diseases such as lung cancer. The 3D novel cell culture system recapitulates stromal-epithelial interactions in vitro that can be utilized to understand important aspects of lung development and diseases.
Department of Cell Biology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Aadil
A
Kaisani
Department of Cell Biology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Oliver
O
Delgado
Department of Cell Biology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Gail
G
Fasciani
Department of Cell Biology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Sang Bum
SB
Kim
Department of Cell Biology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Woodring E
WE
Wright
Hamon Center for Therapeutic Oncology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA; Department of Internal Medicine, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA; Department of Pharmacology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
John D
JD
Minna
Department of Cell Biology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA; Center for Excellence in Genomics Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: Jerry.Shay@UTSouthwestern.edu.
Jerry W
JW
Shay
D001980:Bronchi / Q000166:cytology* / Q000254:growth & development; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D053686:Fetal Stem Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D008168:Lung / Q000166:cytology; D009024:Morphogenesis; D011509:Proteoglycans / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000166:cytology* / Q000187:drug effects
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen
Branching; Bronchial epithelial cells; Differentiation; Distal airways; Fibroblasts