Paving the Way Toward Complex Blood-Brain Barrier Models Using Pluripotent Stem Cells

A tissue with great need to be modeled in vitro is the blood-brain barrier (BBB). The BBB is a tight barrier that covers all blood vessels in the brain and separates the brain microenvironment from the blood system. It consists of three cell types [neurovascular unit (NVU)] that contribute to the unique tightness and selective permeability of the BBB and has been shown to be disrupted in many diseases and brain disorders, such as vascular dementia, stroke, multiple sclerosis, and Alzheimer's disease. Given the progress that pluripotent stem cells (PSCs) have made in the past two decades, it is now possible to produce many cell types from the BBB and even partially recapitulate this complex tissue in vitro. In this review, we summarize the most recent developments in PSC differentiation and modeling of the BBB. We also suggest how patient-specific human-induced PSCs could be used to model BBB dysfunction in the future. Lastly, we provide perspectives on how to improve production of the BBB in vitro, for example by improving pericyte differentiation protocols and by better modeling the NVU in the dish.