Chapter 3 - In vitro blood–brain barrier model derived from human iPS cells and its applications

Abstract

The blood–brain barrier (BBB) is the interface between the surrounding blood circulation and the nervous tissue in the brain, maintaining brain homeostasis by regulating the transport of substances between the cardiovascular system and the central nervous system (CNS). The BBB is composed of brain microvascular endothelial cells (BMECs), which are linked together by tight junctions (TJ), forming a physical paracellular barrier. A series of specialized transporters and efflux pumps regulates the transcellular transport of various substances, protecting the brain from foreign substances and maintaining the homeostasis of the brain. In addition, BMECs are structurally and functionally supported by other components in the neurovascular unit (NVU), such as pericytes, astrocytes, and basement membranes, and the interactions among components in the NVU contribute to the maintenance and development of BBB. Since the impaired BBB function has been observed in several neurological diseases, it is important to build a reliable in vitro BBB model for the research of disease mechanisms and CNS drug development. Induced pluripotent stem cells (iPSCs) raise concerns as an ideal cell source for in vitro BBB modeling given their human origin, scalability, and potential to generate syngeneic cellular components of the NVU. In this chapter, the schemes in differentiating iPSCs into BMECs, the key step in BBB modeling, are discussed. Additionally, several applications of iPSCs-BBB model will also be introduced.