Dr. Moriah Katt

Modeling the blood-brain barrier in ischemic stroke. The blood-brain barrier(BBB) is made up of the blood vessels in the brain and the surrounding supporting cells making up the neurovascular unit. It plays the critical role of protecting the delicate environment in the brain and maintaining brain homeostasis. It accomplishes this by transporting nutrients, amino acids, and all other needed substances into the brain while excluding nearly everything else. Modeling the BBB is complex and difficult, with many different potential influences including cell source, co-culture with supporting cells, and incorporation of physiological blood flow. Selecting the right mixture of conditions to accurately replicate the BBB while not overcomplicating the system and maintaining replicability.  The BBB undergoes significant functional changes in the aftermath of ischemic stroke. These phenotypic changes impair its ability to maintain brain homeostasis and prevent further damage to the delicate brain parenchyma. Existing models of this have failed to capture the dynamics of this disruption is critical for disease understanding and for therapeutic delivery. Development of a human based model is critical for development of novel therapeutics to aid in recovery following an ischemic stroke. Using a human induced pluripotent stem cell (hiPSC) derived model of the BBB using brain endothelial-like cells (BMECs), pericyte-, and astrocyte-like cells all derived from a single hiPSC line an isogenic model of the BBB was produced. This model was then exposed to simulated ischemia conditions including hypoxia and glucose deprivation in a variety of culture conditions to replicate BBB dysfunction in ischemic stroke. Using a mixture of culture techniques, the parameter space is explored to identify the appropriate set of experimental components to best recapitulate the complex environment of ischemic stroke. Ultimately these results allow us to identify novel therapeutic targets in ischemic stroke for improved patient outcome.