Exploiting the potential of lung stem cells to develop pro-regenerative therapies

ABSTRACT Acute and chronic lung diseases are a leading cause of morbidity and mortality globally. Unfortunately, these diseases are increasing in frequency and we have limited treatment options for severe lung diseases. New therapies are needed that not only treat symptoms or slow disease progression, but also enable the regeneration of functional lung tissue. Both airways and alveoli contain populations of epithelial stem cells with the potential to self-renew and produce differentiated progeny. Understanding the mechanisms that determine the behaviour of these cells, and their interactions with their niches, will allow future generations of respiratory therapies that protect the lungs from disease onset, promote regeneration from endogenous stem cells or enable regeneration through the delivery of exogenous cells. This review summarises progress towards each of these goals, highlighting the challenges and opportunities of developing pro-regenerative (bio)pharmaceutical, gene and cell therapies for respiratory diseases.