Reconstructing the pulmonary niche with stem cells: a lung story

The global burden of pulmonary disease highlights an overwhelming need in improving our understanding of lung development, disease, and treatment. It also calls for further advances in our ability to engineer the pulmonary system at cellular and tissue levels. The discovery of human pluripotent stem cells (hPSCs) offsets the relative inaccessibility of human lungs for studying developmental programs and disease mechanisms, all the while offering a potential source of cells and tissue for regenerative interventions. This review offers a perspective on where the lung stem cell field stands in terms of accomplishing these ambitious goals. We will trace the known stages and pathways involved in in vivo lung development and how they inspire the directed differentiation of stem and progenitor cells in vitro. We will also recap the efforts made to date to recapitulate the lung stem cell niche in vitro via engineered cell–cell and cell-extracellular matrix (ECM) interactions.