Editors' ChoiceOrgan Transplantation

The Making of a New Lung

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Science Translational Medicine  25 Aug 2010:
Vol. 2, Issue 46, pp. 46ec134
DOI: 10.1126/scitranslmed.3001603

Lung transplantation remains the treatment of choice for disabling end-stage lung disease from chronic obstructive pulmonary disease, cystic fibrosis, idiopathic pulmonary fibrosis, and pulmonary hypertension. However, the supply of donor lungs is severely limited, and only one out of three patients on the waiting list undergo transplantation. Outcomes after lung transplantation are further impaired by chronic rejection by the recipient’s immune system and the adverse effects of immunosuppressive therapies. Now, Ott et al. seek to engineer a functional bioartificial lung that can be transplanted without the concern for immunologic rejection.

The authors first removed cells from cadaveric lungs using detergent perfusion, leaving a decellularized whole-lung scaffold composed of extracellular matrix proteins. The extracellular matrix not only defines the lung’s architecture and physical properties, but also plays a critical role in pulmonary cell differentiation. The lung scaffold was then repopulated by incubation with fetal lung cells and human umbilical cord endothelial cells. The microanatomy of regenerated lung constructs resembled the native lung and demonstrated nearly physiologic ventilation mechanics and gas exchange capacity in vitro. Upon transplantation into rats, the regenerated lung restored gas exchange and allowed the animals to breathe without ventilatory support for up to 6 hours.

This proof-of-concept study by Ott et al. has demonstrated that viable, bioartificial lungs can be generated, providing functional gas exchange in vitro and in vivo. The differentiation and maturation of cells in the regenerated lung graft, however, will require further investigation—for instance, the bioartificial lungs developed pulmonary edema just hours after transplantation, which is probably secondary to the lack of lymphatics and/or capillary leak from immature blood vessels. Nonetheless, the generation of bioartificial lung grafts represents a promising strategy for increasing the organ supply for transplantation in the treatment of end-stage lung diseases.

H. C. Ott et al., Regeneration and orthotopic transplantation of a bioartificial lung. Nat. Med. 16, 927–933 (2010). [Abstract]

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