Microphysiological systems: Probing Neurological Disease

Many of the most debilitating and life-threatening diseases are associated with the central nervous system. Some, such as neurodegenerative diseases, predominately afflict our aging population. Yet others such as brain cancers and ALS are prevalent at all ages. In this presentation, several models will be presented that attempt to recapitulate certain aspects of the central or peripheral nervous system, both to probe the disease process, and as a platform to screen for new therapeutics. Examples will be presented selected from the following: 1) A model for the healthy blood-brain barrier and neurovascular unit has been developed in order to capture the essential aspects of barrier impairment in disease. 2) The blood-brain barrier model is used to study metastasis of cancers to the brain, identifying the critical role of astrocyte-secreted CCL2 in tumor cell extravasation. 3) A model for the healthy and diseased neuromuscular junction will be presented as a step toward developing therapeutic strategies for treating ALS.  4) A model for cerebral amyloid angiopathy, often associated with Alzheimer’s disease, will be discussed as a disease model and its drug screening potential.  Time-permitting, translation of these models to screening platforms and potential barriers will be discussed.

Learning Objectives:

1. Understand how primary and iPS cell-derived cells can be used to develop 3D in vitro models of organ function and disease

2. Learn about the different types of microphysiological systems using 3D hydrogels and relying on cellular self-organization and self-assembly

3. Identify some of the barriers to generating fully-functional, user-friendly models in moderate throughput platforms