Organ-specific endothelial cell heterogenicity and its impact on regenerative medicine and biomedical engineering applications.

Endothelial cells (ECs) are a key cellular component of the vascular system as they form the inner lining of the blood vessels. Recent findings highlight that ECs express extensive phenotypic heterogenicity when following the vascular tree from the major vasculature down to the organ capillaries. However, in vitro models, used for drug development and testing, or to study the role of ECs in health and disease, rarely acknowledge this EC heterogenicity. In this review, we highlight the main differences between different EC types, briefly summarize their different characteristics and focus on the use of ECs in in vitro models. We introduce different approaches on how ECs can be utilized in co-culture test systems in the field of brain, pancreas, and liver research to study the role of the endothelium in health and disease. Finally, we discuss potential improvements to current state-of-the-art in vitro models and future directions.