Elsevier

The Annals of Thoracic Surgery

Volume 92, Issue 3, September 2011, Pages 998-1006
The Annals of Thoracic Surgery

TSDA Benson R. Wilcox award
Enhanced In Vivo Function of Bioartificial Lungs in Rats

Presented at the Forty-seventh Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 31–Feb 2, 2011. Winner of the Thoracic Surgery Directors Association Benson R. Wilcox Award.
https://doi.org/10.1016/j.athoracsur.2011.05.018Get rights and content

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.

Section snippets

Perfusion-Decellularized Native Lung Scaffolds

All animal experiments were approved by the Massachusetts General Hospital Institutional Animal Care and Use Committee and performed in compliance with the Animal Welfare Act. Cadaveric rat lungs were perfusion-decellularized as previously described [5]. In brief, systemically heparinized (American Pharmaceutical Partners, Schaumburg, IL) male Sprague-Dawley rats weighing 260 g to 280 g (Charles River Labs, Boston, MA) were euthanized through intraperitoneal pentobarbital injection. Cadaveric

Results

Detergent perfusion and washing of cadaveric rat lungs with physiologic perfusion pressure resulted in acellular lung ECM scaffolds with intact ECM architecture, and preserved ECM composition, as previously described [5]. The resulting scaffolds could be mounted in a bioreactor system, seeded with endothelial cells through pulmonary artery and vein, and fetal lung cells through trachea. Cell-seeded constructs could be subsequently exposed to biomimetic culture conditions, including media

Comment

Lung transplantation is the only potentially curative option for end-stage lung disease, yet donor organs are short, and side effects of immunosuppression and chronic rejection limit its clinical impact. A bioartificial lung graft derived from immunotolerated materials such as acellular scaffolding and autologous cells that can be implanted in orthotopic position is a theoretical alternative to allotransplantation. Recent reports on successful clinical implantation of airway grafts derived from

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