Lung Regeneration - Approaches

Lung disease is currently only one of the top three causes of death in the U.S. that is increasing in prevalence. The most effective method of ameliorating end-stage lung disease is lung transplant. However, this intervention has relatively poor outcomes compared to transplant of other organs, with survival of only 30% at the 10 year mark, and suffers from a paucity of organs that are viable for transplant. Whole organ engineering offers an avenue for reducing organ shortage and, ultimately, to improve transplant outcomes by the use of autologous cells to engineer tissue.

Our lab has previously demonstrated the ability to generate acellular lung extracellular matrix scaffolds for use in lung tissue engineering (Petersen et al., 2011). Using a biomimetic bioreactor that provides access to the airway and vascular compartments of the lung independently, we are able to generate lung tissue that can exchange gas for several hours upon implantation in vivo. Ultimately, however, these implanted tissues failed due to incomplete barrier formation between air and blood and to thrombosis of the microvasculature upon exposure to blood. Optimization of recellularization to improve cellular coverage of the extracellular matrix in whole lung scaffolds and advancement of bioreactor culture methods is required to enhance the function of bioengineered lungs. The challenge now lies in augmenting cell-cell junctions that will confer sufficient barrier function to be compatible with long-term function in vivo.

Petersen, T.H., Calle, E.A., Colehour, M.B., and Niklason, L.E. (2011). Bioreactor for the long-term culture of lung tissue. Cell Transplant 20, 1117-1126.