Bioengineering Lungs for Transplantation
Lung transplantation, at one time, seemed like science fiction, but innovations in surgical technique and immunosuppression made it clinical reality. Limited supply of donor lungs and the vagaries of immunosuppression still limit its success.
A pair of articles published last year has created an aura of science fiction once again (Ott et al. Nat Med. 2010;16[8]:927; Petersen et al. Science. 2010;329[5991]:538). Two groups of researchers developed an engineered lung through decellularization and recellularization in a rat model. In the experiments, an explanted adult rat lung was decellularized with a detergent, creating a sort of scaffolding of the lung. It retained its ultrastructural properties with complete removal of antigenic cellular components. Preservation of lung architecture and microvasculature was seen on CT imaging. Even the alveolar septal architecture remained undisturbed.
This acellular matrix was mounted inside a biomimetic bioreactor, where fetal vascular endothelium could be seeded into the pulmonary artery and fetal pulmonary epithelium into the trachea. Inside the bioreactor, the lungs were perfused with blood and ventilated at physiologic pressures, with gas exchange comparable to native lungs under the same conditions. After 4 to 8 days of culture, the lungs were removed and successfully implanted into syngeneic rats where selective blood gas analysis demonstrated gas exchange in the engineered lungs.
Tissue-engineered lungs could alleviate donor availability and many of the allo-immunity problems, if such a concept could be developed to clinical reality. There are many hurdles to overcome, but along with other novel concepts, such as a microchip that performs gas exchange (Science. 2010 Jun 25; 328(5986):1662), we must wonder what the future holds for such technologies.
One of the lead researchers, Dr. Tom Peterson, will discuss the topic, “Tissue-Engineered Lungs for In Vivo Implantation” at the Transplant NetWork open meeting on Monday, October 24, at 7:15 am in the Honolulu Convention Center, room 318B.
Dr. Daniel Dilling, FCCP
NetWork Steering Committee Member
NetWork Steering Committee Member
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