In vitro Blood Brain Barrier Models

Over 600 diseases that damage the central nervous system (CNS) have been identified but relatively few treatments exist. Despite significant investment by many researchers, there have not been any successful protein-based medicines developed to treat brain diseases including Alzheimer’s. There are many reasons why therapeutics to treat brain diseases do not exist but one major pitfall lies in the current drug development pipeline. Preclinical screening of new drugs is performed using overly simplified in vitro models followed by animal testing. Unfortunately, these screening approaches do not accurately recapitulate transport in the human brain and drugs that pass preclinical screening often fail in humans. This dismal success rate indicates a clear need for superior preclinical screening models. The National Institutes of Health has recognized this problem and recently started a Tissue Chip for Drug Screening Program with the hopes of creating microfluidic in vitro drug screening models that more accurately recapitulate transport in the human body than existing models. Toward this goal, we are developing a three dimensional, microfluidic in vitro blood brain barrier model that more accurately recapitulates transport in the human brain by (i) utilizing human BMECs that express the proper transporters, (ii) induction and maintenance of BBB function via applied shear, and (iii) use of 3D microfluidic networks derived from the vascular architecture of the human brain. Implementation of this model will aid preclinical screening of brain-specific therapeutics leading to increased clinical success as well as lay a foundation for development of in vitro culture models of CNS diseases. This work is performed in collaboration with Dr. Kelvin Lee in the Department of Chemical & Biomolecular Engineering at the University of Delaware.

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Smith et al. “Brain Capillary Networks Across Species: A Few Simple Organizational Requirements are Sufficient to Reproduce Both Structure and Function.” Frontiers in Physiology. 2019.