Chapter 14 - Challenges and opportunities for regenerating lung tissue using three-dimensional lung models

Abstract

Lung transplantation is currently the only option for patients with end-stage respiratory diseases, but owing to various complications and adverse effects of the treatment in combination with the increasing demand for and limited access to donor organs, new strategies are needed. Recent advances in materials science, culture techniques, cell-phenotyping and isolation techniques, bioreactor engineering, and imaging techniques have opened up new possibilities for generating advanced three-dimensional lung models. The lung is a complex organ to rebuild, consisting of more than 40 different cell types working together to create a functional unit that allows for proper gas exchange and protection against the external environment. However, it is well known that the cells do not work alone. It was long thought that the only function of the extracellular matrix (ECM) was to provide the organ and cells with structural support, but we now know that the ECM plays a much more vital role. Despite this knowledge, the majority of studies are still performed by using traditional two-dimensional (2D) cultures on plastic. There are, of course, occasions when 2D cultures are necessary; however, it is important to remember that essential features, including orientation, mechanical properties, and cell-cell and cell-matrix interactions, are missing. These are important properties that will most likely affect the final results and the possibility of translating in vitro findings into in vivo models.