reconstruction-blood-brain-barrier-vitro-to-model-therapeutically

Reconstruction of the Blood-Brain Barrier <em>In Vitro</em> to Model and Therapeutically Target Neurological Disease

The blood-brain barrier (BBB) is a key physiological component of the central nervous system (CNS), maintaining nutrients, clearing waste, and protecting ...

Icahn School of Medicine at Mount Sinai

Black Family Stem Cell Institute at Mount Sinai

Ronald M. Loeb Center for Alzheimer’s Disease at Mount Sinai

Friedman Brain Institute at Mount Sinai

Nash Family Department of Neuroscience at Mount Sinai

The blood-brain barrier (BBB) is a key physiological component of the brain, protecting the brain from peripheral processes and pathogens. The BBB is a dynamic structure that is heavily involved in cerebral blood flow, angiogenesis, and other neural functions. However, the BBB also creates a challenging barrier for the entry of therapeutics into the brain, blocking more than 98% of drugs from contact with the brain. Neurovascular comorbidities are common in several neurological diseases including Alzheimer's and Parkinson's Disease, suggesting that BBB dysfunction or break down likely has a causal role in neurodegeneration. However, the mechanisms by which the human BBB is formed, maintained, and degenerated in diseases remain largely unknown due to limited access to human BBB tissue. To address these limitations, we have developed an in vitro induced human BBB (iBBB) derived from pluripotent stem cells. The iBBB model can be used for discovery of disease mechanisms, drug targets, drug screening, and medicinal chemistry studies to optimize brain penetration of central nervous system therapeutics. In this chapter, we will explain the steps to differentiate the three cellular components (endothelial cells, pericytes, and astrocytes) from induced pluripotent stem cells, and how to assemble them into the iBBB.

Joel W. Blanchard

Icahn School of Medicine at Mount Sinai

Reconstruction of the Blood-Brain Barrier In Vitro to Model and Therapeutically Target Neurological Disease