Regenerative potential of human airway stem cells in lung epithelial engineering

Abstract Bio-engineered organs for transplantation may ultimately provide a personalized solution for end-stage organ failure, without the risk of rejection. Building upon the process of whole organ perfusion decellularization, we aimed to develop novel, translational methods for the recellularizati...

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Bibliographic Details
Published in:Biomaterials 2016-11, Vol.108, p.111-119
Main Authors: Gilpin, Sarah E, Charest, Jonathan M, Ren, Xi, Tapias, Luis F, Wu, Tong, Evangelista-Leite, Daniele, Mathisen, Douglas J, Ott, Harald C
Format: Article
Language:English
Subjects:
Advanced Basic Science
Bioartificial Organs
Bioengineering
Cells, Cultured
Construction
Culture
Decellularization
Dentistry
Epithelial Cells - cytology
Epithelial Cells - physiology
Epithelial repair
Extracellular matrix
Humans
Lung - cytology
Lung - growth & development
Lung tissue engineering
Lungs
Organs
Recellularization
Regeneration
Regeneration - physiology
Regenerative
Respiratory Mucosa - cytology
Respiratory Mucosa - physiology
Scaffolds
Stem cells
Tissue Engineering - instrumentation
Tissue Engineering - methods
Tissue Scaffolds
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Summary:Abstract Bio-engineered organs for transplantation may ultimately provide a personalized solution for end-stage organ failure, without the risk of rejection. Building upon the process of whole organ perfusion decellularization, we aimed to develop novel, translational methods for the recellularization and regeneration of transplantable lung constructs. We first isolated a proliferative KRT5+ TP63+ basal epithelial stem cell population from human lung tissue and demonstrated expansion capacity in conventional 2D culture. We then repopulated acellular rat scaffolds in ex vivo whole organ culture and observed continued cell proliferation, in combination with primary pulmonary endothelial cells. To show clinical scalability, and to test the regenerative capacity of the basal cell population in a human context, we then recellularized and cultured isolated human lung scaffolds under biomimetic conditions. Analysis of the regenerated tissue constructs confirmed cell viability and sustained metabolic activity over 7 days of culture. Tissue analysis revealed extensive recellularization with organized tissue architecture and morphology, and preserved basal epithelial cell phenotype. The recellularized lung constructs displayed dynamic compliance and rudimentary gas exchange capacity. Our results underline the regenerative potential of patient-derived human airway stem cells in lung tissue engineering. We anticipate these advances to have clinically relevant implications for whole lung bioengineering and ex vivo organ repair.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2016.08.055