Comparison of organ-specific endothelial cells in terms of microvascular formation and endothelial barrier functions

摘要

Every organ demonstrates specific vascular characteristics and functions maintained by interactions of endothelial cells (ECs) and parenchymal cells. Particularly, brain ECs play a central role in the formation of a functional blood brain barrier (BBB). Organ-specific ECs have their own morphological features, and organ specificity must be considered when investigating interactions between ECs and other cell types constituting a target organ. Here we constructed angiogenesis-based microvascular networks with perivascular cells in a microfluidic device setting by coculturing ECs and mesenchymal stem cells (MSCs). Furthermore, we analyzed endothelial barrier functions as well as fundamental morphology, an essential step to build an in vitro BBB model. In particular, we used both brain microvascular ECs (BMECs) and human umbilical vein ECs (HUVECs) to test if organ specificity of ECs affects the formation processes and endothelial barrier functions of an engineered microvascular network. We found that microvascular formation processes differed by the source of ECs. HUVECs formed more extensive microvascular networks compared to BMECs while no differences were observed between BMECs and HUVECs in terms of both the microvascular diameter and the number of pericytes peripherally associated with the microvasculatures. To compare the endothelial barrier functions of each type of EC, we performed fluorescence dextran perfusion on constructed microvasculatures. The permeability coefficient of BMEC microvasculatures was significantly lower than that of HUVEC microvasculatures. In addition, there were significant differences in terms of tight junction protein expression. These results suggest that the organ source of ECs influences the properties of engineered microvasculature and thus is a factor to be considered in the design of organ-specific cell culture models.