title: Tissue-engineered lungs for in vivo implantation.
abstract: Because adult lung tissue has limited regeneration capacity, lung transplantation is the primary therapy for severely damaged lungs. To explore whether lung tissue can be regenerated in vitro, we treated lungs from adult rats using a procedure that removes cellular components but leaves behind a scaffold of extracellular matrix that retains the hierarchical branching structures of airways and vasculature. We then used a bioreactor to culture pulmonary epithelium and vascular endothelium on the acellular lung matrix. The seeded epithelium displayed remarkable hierarchical organization within the matrix, and the seeded endothelial cells efficiently repopulated the vascular compartment. In vitro, the mechanical characteristics of the engineered lungs were similar to those of native lung tissue, and when implanted into rats in vivo for short time intervals (45 to 120 minutes) the engineered lungs participated in gas exchange. Although representing only an initial step toward the ultimate goal of generating fully functional lungs in vitro, these results suggest that repopulation of lung matrix is a viable strategy for lung regeneration.
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Petersen
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Calle
authors.forename: Liping
authors.initials: L
authors.lastname: Zhao
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Lee
authors.forename: Liqiong
authors.initials: L
authors.lastname: Gui
authors.forename: MichaSam B
authors.initials: MB
authors.lastname: Raredon
authors.forename: Kseniya
authors.initials: K
authors.lastname: Gavrilov
authors.forename: Tai
authors.initials: T
authors.lastname: Yi
authors.forename: Zhen W
authors.initials: ZW
authors.lastname: Zhuang
authors.forename: Christopher
authors.initials: C
authors.lastname: Breuer
authors.forename: Erica
authors.initials: E
authors.lastname: Herzog
authors.forename: Laura E
authors.initials: LE
authors.lastname: Niklason
mesh_terms: D000818:Animals; D019149:Bioreactors; D003902:Detergents; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000166:cytology / Q000502:physiology; D008170:Lung Compliance; D016040:Lung Transplantation; D008297:Male; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000648:ultrastructure; D011659:Pulmonary Gas Exchange; D051381:Rats; D011916:Rats, Inbred F344; D012038:Regeneration; D020545:Respiratory Mucosa / Q000166:cytology; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D003902:Detergents