Tissue-engineered lungs for in vivo implantation.
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.
Petersen
Thomas H
TH
Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
Calle
Elizabeth A
EA
Zhao
Liping
L
Lee
Eun Jung
EJ
Gui
Liqiong
L
Raredon
MichaSam B
MB
Gavrilov
Kseniya
K
Yi
Tai
T
Zhuang
Zhen W
ZW
Breuer
Christopher
C
Herzog
Erica
E
Niklason
Laura E
LE
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
D003902:Detergents