TY - JOUR
T1 - Enhanced in vivo function of bioartificial lungs in rats
AU - Song, Jeremy J.
AU - Kim, Sam S.
AU - Liu, Zhilin
AU - Madsen, Joren C.
AU - Mathisen, Douglas J.
AU - Vacanti, Joseph P.
AU - Ott, Harald C.
N1 - Funding Information:
We thank Harvard Apparatus for providing bioreactor components, technical advice, and prototype manufacturing. We thank Jim Titus for technical assistance with animal surgeries and video recording. This study was supported by a Faculty Development Grant provided by the Department of Surgery (to H.C.O.), Massachusetts General Hospital, by a Young Clinician Researcher Award granted by the Center for Integration of Medicine and Innovative Technology (to H.C.O.), by an American Heart Association Predoctoral Fellowship (to J.J.S., 10PRE3870031), and by the Massachusetts General Hospital Summer Scholar Program in Thoracic Surgery (to J.J.S.).
PY - 2011/9
Y1 - 2011/9
N2 - Background: More than 11 million Americans live with chronic lung disease; in search for an alternative to donor organs, we attempted to regenerate lungs based on perfusion decellularized lung scaffolds that can be transplanted similar to a donor organ. Methods: Cadaveric rat lungs were decellularized by detergent perfusion. Resulting scaffolds were mounted in bioreactors and seeded with endothelial and fetal lung cells. Biomimetic organ culture was maintained for 7 days. Resulting bioartificial left lungs were transplanted in orthotopic position after left pneumonectomy in rats. Cadaveric left lung transplants and pneumonectomies served as controls. Blood gas analyses, compliance testing, and fluoroscopies were performed on postoperative days 1, 7, and 14. Lungs were removed for final analysis on day 14. Results: Perfusion decellularization of cadaveric lungs yielded acellular scaffolds with intact architecture and matrix composition. Alveolar volumes, number, and size were comparable in bioartificial and native lungs, as were gas exchange, vital capacity and compliance in vitro. After using improved graft preservation and postoperative weaning protocols, animals could be fully recovered, and bioartificial lung constructs provided oxygenation as long as 7 days at levels comparable to cadaveric lung transplants. Compliance, gas exchange, and radiographic appearance gradually declined over the subsequent 7 days owing to progressive graft consolidation and inflammation. Conclusions: Perfusion decellularization of cadaveric lungs yields intact scaffolds that can be seeded with cells to generate bioartificial lung grafts. After orthotopic transplantation, grafts are perfused by the recipient's circulation, ventilated through the recipient's airway and provide gas exchange in vivo for 7 days.
AB - Background: More than 11 million Americans live with chronic lung disease; in search for an alternative to donor organs, we attempted to regenerate lungs based on perfusion decellularized lung scaffolds that can be transplanted similar to a donor organ. Methods: Cadaveric rat lungs were decellularized by detergent perfusion. Resulting scaffolds were mounted in bioreactors and seeded with endothelial and fetal lung cells. Biomimetic organ culture was maintained for 7 days. Resulting bioartificial left lungs were transplanted in orthotopic position after left pneumonectomy in rats. Cadaveric left lung transplants and pneumonectomies served as controls. Blood gas analyses, compliance testing, and fluoroscopies were performed on postoperative days 1, 7, and 14. Lungs were removed for final analysis on day 14. Results: Perfusion decellularization of cadaveric lungs yielded acellular scaffolds with intact architecture and matrix composition. Alveolar volumes, number, and size were comparable in bioartificial and native lungs, as were gas exchange, vital capacity and compliance in vitro. After using improved graft preservation and postoperative weaning protocols, animals could be fully recovered, and bioartificial lung constructs provided oxygenation as long as 7 days at levels comparable to cadaveric lung transplants. Compliance, gas exchange, and radiographic appearance gradually declined over the subsequent 7 days owing to progressive graft consolidation and inflammation. Conclusions: Perfusion decellularization of cadaveric lungs yields intact scaffolds that can be seeded with cells to generate bioartificial lung grafts. After orthotopic transplantation, grafts are perfused by the recipient's circulation, ventilated through the recipient's airway and provide gas exchange in vivo for 7 days.
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U2 - 10.1016/j.athoracsur.2011.05.018
DO - 10.1016/j.athoracsur.2011.05.018
M3 - Article
C2 - 21871290
AN - SCOPUS:80052786772
SN - 0003-4975
VL - 92
SP - 998
EP - 1006
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 3
ER -