Heterogeneous potential of human airway basal cells: Holoclone-stem cell identification in a clinical-grade system

Abstract

ABSTRACTThe clinical results of tissue engineering approaches aimed at treating extensive tracheal or bronchial defects highlighted some impactful limitations, among which stand out the inability to regenerate a functional and self-renewing airway epithelium onto the bioengineered graft. This outcome is often caused by culture conditions unable to sustain the long-term proliferative and differentiative potential of primary airway epithelial cells, resulting in progressive stem cell exhaustion. Here, we examined the capacity of a clinical-grade culture system to safely and efficiently support thein vitroexpansion of primary human tracheal and bronchial epithelial cells, regenerating a functional and fully differentiated airway epithelium. Moreover, we identified and characterized airway epithelial stem cells, unravelling the mechanisms that underlie tracheobronchial epithelium renewal. Finally, we suggested possible parameters to be employed as quality controls during critical stages of the tissue engineering process, thereby maximizing the likelihood of success of the treatment and prioritizing patients’ safety, crucial prerequisites before embarking on other clinical applications.GRAPHICAL ABSTRACT