The Impact of Oxygen Availability and Multilineage Communication on Organoid Maturation

An optimal supply with oxygen is of high importance during embryogenesis and a prerequisite for proper organ development. Different tissues require varying amounts of oxygen, and even within single organs, different phases of development go alongside with either physiological hypoxia or the need for sufficient oxygen supply. Human induced pluripotent stem cell-derived organoid models are state of the art cell culture platforms for the investigation of developmental processes, disease modeling, and drug testing. Organoids modeling the development of multiple tissues were developed within the past years. Until now, optimization of oxygen supply and its role during organoid growth, differentiation, and maturation have only rarely been addressed. Recent publications indicate that hypoxia-induced processes play an important role in three-dimensional tissue cultures, triggering multilineage communication between mesenchymal cells, the endothelium, as well as organotypic cells. Later in culture, a sufficient supply with oxygen is of high importance to allow larger organoid sizes. Moreover, cellular stress is reduced and tissue maturation is improved. Therefore, a functional blood vessel network is required. In this review, we will briefly summarize aspects of the role of oxygen during embryonic development and organogenesis, present an update on novel organoid models with a special focus on organoid vascularization, and discuss the importance of complex organoids involving parenchymal cells, mesenchymal cells, inflammatory cells, and functional blood vessels for the generation of mature and fully functional tissues in vitro. Antioxid. Redox Signal. 35, 217-233.