The mechanical microenvironment and lung stem cell fate

The lung is a complex, branched organ that follows an intricate and well-coordinated developmental process to generate dozens of different cell types. Several protocols have been established to differentiate stem cells into the cell types of the lung in culture, to complement studies in animals aimed at understanding the basic processes of lung development, homeostasis, and response to injury. However, these protocols are generally both inefficient and poorly reproducible. To improve current differentiation protocols, it is important to consider how lung epithelial cells interact with their surrounding biochemical and mechanical microenvironment during development in the embryo. In this review, we describe the different microenvironmental signals that promote growth and differentiation of lung progenitors and mature lung epithelial cells. We also highlight the specific mechanical components of the microenvironment that have been recently used in cell culture models. We postulate that understanding and incorporating combinations of these microenvironmental signals to better mimic the mechanical niche can increase the efficiency, reproducibility, and physiological accuracy of culture models of the lung.