title: Lung bioengineering: physical stimuli and stem/progenitor cell biology interplay towards biofabricating a functional organ.
abstract: A current approach to obtain bioengineered lungs as a future alternative for transplantation is based on seeding stem cells on decellularized lung scaffolds. A fundamental question to be solved in this approach is how to drive stem cell differentiation onto the different lung cell phenotypes. Whereas the use of soluble factors as agents to modulate the fate of stem cells was established from an early stage of the research with this type of cells, it took longer to recognize that the physical microenvironment locally sensed by stem cells (e.g. substrate stiffness, 3D architecture, cyclic stretch, shear stress, air-liquid interface, oxygenation gradient) also contributes to their differentiation. The potential role played by physical stimuli would be particularly relevant in lung bioengineering since cells within the organ are physiologically subjected to two main stimuli required to facilitate efficient gas exchange: air ventilation and blood perfusion across the organ. The present review focuses on describing how the cell mechanical microenvironment can modulate stem cell differentiation and how these stimuli could be incorporated into lung bioreactors for optimizing organ bioengineering.
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Casanova 143, 08036, Barcelona, Spain.
authors.forename: Paula N
authors.initials: PN
authors.lastname: Nonaka
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Casanova 143, 08036, Barcelona, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Uriarte
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Casanova 143, 08036, Barcelona, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Campillo
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Casanova 143, 08036, Barcelona, Spain.
authors.forename: Vinicius R
authors.initials: VR
authors.lastname: Oliveira
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Casanova 143, 08036, Barcelona, Spain.|CIBER Enfermedades Respiratorias, Madrid, Spain.|Institut de Bioenginyeria de Catalunya, Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Navajas
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Casanova 143, 08036, Barcelona, Spain. rfarre@ub.edu.|CIBER Enfermedades Respiratorias, Madrid, Spain. rfarre@ub.edu.|Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain. rfarre@ub.edu.
authors.forename: Ramon
authors.initials: R
authors.lastname: Farré
mesh_terms: D000818:Animals; D001187:Artificial Organs; D057005:Bioengineering / Q000379:methods*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology; D023822:Tissue Engineering
keywords: Bioreactor; Lung scaffolds; Mechanical microenvironment; Organ bioengineering; Physical stimuli; Stem cell