In vitro blood-brain barrier reconstruction model (BBB Kit) and their application to the functional analysis

血脑屏障(BBB)是神经血管单位(NVU)的一员，在脑毛细血管内皮细胞与其他邻近细胞如星形胶质细胞和周细胞之间起通讯作用。目前正在开发的许多药物旨在发挥中枢作用，但它们没有通过血脑屏障。此外，血脑屏障与参与NVU的相关细胞之间的串扰仍有待阐明。在利用大鼠原代脑毛细血管内皮细胞、周细胞和星形胶质细胞建立三重共培养血脑屏障模型(BBB Kit)的基础上，我们成功地用原代猴脑毛细血管内皮细胞、大鼠周细胞和大鼠星形胶质细胞建立了猴血脑屏障的体外模型，用于筛选候选药物的血脑屏障渗透和血脑屏障病理生理学研究。此外，我们还建立了由猪脑毛细血管内皮细胞、大鼠周细胞和大鼠星形胶质细胞组成的猪血脑屏障模型。

The blood-brain barrier (BBB), a member of the neurovascular unit (NVU), functions in communication between brain capillary endothelial cells and other neighboring cells such as astrocytes and pericytes. Many drugs that are currently under development are intended to act centrally, but they do not cross the BBB. Furthermore, the crosstalk between the BBB and related cells contributing to the NVU remains to be elucidated. Based on our breakthrough in using rat primary brain capillary endothelial cells, pericytes and astrocytes to create a triple co-culture BBB model (BBB Kit), an in vitro models for screening the BBB penetration of drug candidates and research on BBB pathophysiology, we succeeded in modeling the monkey BBB with primary monkey brain capillary endothelial cells, rat pericytes and rat astrocytes. In addition, we constructed a porcine BBB model consisting of porcine brain capillary endothelial cells, rat pericytes, and rat astrocytes