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Sci Adv. 2017 Aug 30;3(8):e1700521. doi: 10.1126/sciadv.1700521. eCollection 2017 Aug.

Functional vascularized lung grafts for lung bioengineering.

Author information

1
Department of Pediatrics, Columbia University Medical Center, New York, NY 10032, USA.
2
Department of Biomedical Engineering, Columbia University Medical Center, New York, NY 10032, USA.
3
Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA.
4
Columbia Center for Human Development, Columbia University Medical Center, New York, NY 10032, USA.
5
Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
6
Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
7
Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.
8
Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.

Abstract

End-stage lung disease is the third leading cause of death worldwide, accounting for 400,000 deaths per year in the United States alone. To reduce the morbidity and mortality associated with lung disease, new therapeutic strategies aimed at promoting lung repair and increasing the number of donor lungs available for transplantation are being explored. Because of the extreme complexity of this organ, previous attempts at bioengineering functional lungs from fully decellularized or synthetic scaffolds lacking functional vasculature have been largely unsuccessful. An intact vascular network is critical not only for maintaining the blood-gas barrier and allowing for proper graft function but also for supporting the regenerative cells. We therefore developed an airway-specific approach to removing the pulmonary epithelium, while maintaining the viability and function of the vascular endothelium, using a rat model. The resulting vascularized lung grafts supported the attachment and growth of human adult pulmonary cells and stem cell-derived lung-specified epithelial cells. We propose that de-epithelialization of the lung with preservation of intact vasculature could facilitate cell therapy of pulmonary epithelium and enable bioengineering of functional lungs for transplantation.

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