title: Giving new life to old lungs: methods to produce and assess whole human paediatric bioengineered lungs.
abstract: We report, for the first time, the development of an organ culture system and protocols to support recellularization of whole acellular (AC) human paediatric lung scaffolds. The protocol for paediatric lung recellularization was developed using human transformed or immortalized cell lines and single human AC lung scaffolds. Using these surrogate cell populations, we identified cell number requirements, cell type and order of cell installations, flow rates and bioreactor management methods necessary for bioengineering whole lungs. Following the development of appropriate cell installation protocols, paediatric AC scaffolds were recellularized using primary lung alveolar epithelial cells (AECs), vascular cells and tracheal/bronchial cells isolated from discarded human adult lungs. Bioengineered paediatric lungs were shown to contain well-developed vascular, respiratory epithelial and lung tissue, with evidence of alveolar-capillary junction formation. Types I and II AECs were found thoughout the paediatric lungs. Furthermore, surfactant protein-C and -D and collagen I were produced in the bioengineered lungs, which resulted in normal lung compliance measurements. Although this is a first step in the process of developing tissues for transplantation, this study demonstrates the feasibility of producing bioengineered lungs for clinical use. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Internal Medicine, Infectious Diseases, University of Texas Medical Branch (UTMB), Galveston, TX, USA.
authors.forename: Joan E
authors.initials: JE
authors.lastname: Nichols
authors.affiliation: Harvard Apparatus Regenerative Technology, Holliston, MA, USA.
authors.forename: Saverio
authors.initials: S
authors.lastname: La Francesca
authors.affiliation: Department of Microbiology and Immunology, UTMB, Galveston, TX, USA.
authors.forename: Stephanie P
authors.initials: SP
authors.lastname: Vega
authors.affiliation: Department of Internal Medicine, Infectious Diseases, University of Texas Medical Branch (UTMB), Galveston, TX, USA.
authors.forename: Jean A
authors.initials: JA
authors.lastname: Niles
authors.affiliation: Department of Immunology, Weill Cornell Medical College New York, New York, NY, USA.
authors.forename: Lissenya B
authors.initials: LB
authors.lastname: Argueta
authors.affiliation: School of Medicine, UTMB, Galveston, TX, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Riddle
authors.affiliation: Methodist Hospital Research Institute, Houston, TX, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Sakamoto
authors.affiliation: Department of Biomedical Engineering, UTMB, Galveston, TX, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Vargas
authors.affiliation: Department of Biomedical Engineering, UTMB, Galveston, TX, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Pal
authors.affiliation: Shiners Hospital for Children, Galveston, TX, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Woodson
authors.affiliation: Methodist Hospital Research Institute, Houston, TX, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Rhudy
authors.affiliation: Methodist Hospital Research Institute, Houston, TX, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Lee
authors.affiliation: Hospital Clinical Engineering, UTMB, Galveston, TX, USA.
authors.forename: David
authors.initials: D
authors.lastname: Seanor
authors.affiliation: Department of Pathology, UTMB, Galveston, TX, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Campbell
authors.affiliation: Department of Pathology, UTMB, Galveston, TX, USA.
authors.forename: Vicki
authors.initials: V
authors.lastname: Schnadig
authors.affiliation: Department of Anesthesiology, UTMB, Galveston, TX, USA.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Cortiella
mesh_terms: D056809:Alveolar Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001705:Bioprosthesis; D019149:Bioreactors; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000737:chemistry*; D008297:Male; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
keywords: bioengineered organs; bioengineered paediatric lungs; decellularized lung scaffold; human bioengineered lungs; laboratory-grown lungs; laboratory-grown paediatric lungs; platelet-rich plasma; tissue-engineered lungs