Adult lung tissue, which has a limited ability to regenerate, currently can only be replaced by lung transplantation. In addition to being expensive, lung transplantation has a 10-year survival rate of only 10–20%. Moreover, there is a serious shortage of donor organs.

In an effort to develop fully functional tissue-engineered lungs for humans, a team of researchers has regenerated adult rat lung tissue in the lab (Science published online 24 June 2010; doi:10.1126/science.1189345). The researchers implanted these engineered lungs into rats and, for the first time, animals breathed with lab-cultivated lungs.

To produce this lung tissue in vitro, a research team led by Laura Niklason of Yale University (New Haven, CT) used a technique called decellularization. They used detergent to remove the cellular components of lungs, turning the lungs from red to white. The acellular adult rat lungs still maintained extracellular matrix scaffolding consisting of air passages and blood vessels.

Niklason and colleagues rinsed the acellular lungs in culture medium and moved the lungs to a culture bioreactor. They then seeded epithelial cells from newborn rats into the decellularized lungs and allowed the epithelium cells to culture on the acellular matrices for 3–5 days. Next, the researchers seeded the microvascular endothelial cells into the vascular portions of the lungs and allowed the lungs to culture. To mimic some aspects of the fetal environment, the researchers circulated fluid through the lungs. This helped improve endothelial adhesion and survival on the lung matrix. Circulating air through the lungs helped the epithelium survive and helped to clear out airway secretions. Analyses suggested that the scaffold had formed into functional lung tissue.

To test whether these engineered lungs would function, the research team removed the left lungs of four rats and implanted an engineered lung into each of them. Chest X-rays confirmed that the implanted lungs were inflating, though not as much as the right native lungs. Importantly, the implanted lungs were able to effectively exchange oxygen and carbon dioxide. About 2 hours after implantation, small blood clots began to develop in the lung's blood vessels, so the researchers euthanized the rats.

Though these results suggest that it might be possible to use decellularization to engineer human lungs in the laboratory, many issues must be resolved before this strategy can become clinically useful. Most importantly, researchers would need to find a way to cultivate a lung using the recipient's own stem cells.