The use of synthetic degradable or permanent polymers and biomaterials has not yet helped to achieve successful clinical whole-airway replacement. A novel, clinically successful approach involves tissue engineering (TE) replacement using three-dimensional biologic scaffolds composed of allogeneic extracellular scaffolds derived from nonautologous sources and recellularized with autologous stem cells or differentiated cells. In this paper, we discuss this novel approach and review information that can lead to a better understanding of stem cell recruitment and/or mobilization and site-specific tissue protection, which can be pharmacologically boosted in humans.