Tissue Engineering and Regenerative Medicine

Cell therapy has the potential to cure disease through replacement of malfunctioning cells. While the tissue stem cell (TSC) is thought to be the optimal therapeutic cell, transplantation of TSC/progenitor cell mixtures has saved lives. We previously purified the mouse tracheobronchial epithelial TSC and reported that in vitro amplification generated numerous TSC. However, these cultures also contained TSC-derived progenitor cells and TSC re-purification by flow cytometry compromised TSC self-renewal. These limitations forced us to determine if a TSC/progenitor cell mixture would repopulate the injured airway epithelium. We developed a clinically-relevant transplantation protocol and demonstrate that transplanted mouse and human tracheobronchial epithelial TSC/progenitor cell mixtures are 20-25% of airway epithelial cells, actively contribute to epithelial repair and persist for at least 43 days. Two weeks after transplantation, TSC/progenitor cells differentiated into the three major epithelial cell types: Basal, secretory, and ciliated. We concluded that adult tracheobronchial TSC/progenitor cell is an effective cell therapy.