Abstract

Modeling Human CNS Disease with Patient Derived Cells : Combining the Power of Stem Cells and Phenotypic Screening in Drug Discovery

Michael Jackson, Vice President/Adjunct Associate Professor, Sanford Burnham Medical Research Institute

Neurological disease modeling and drug discovery efforts would greatly benefit from human cell-based platforms to study neuronal networks and synaptic plasticity. We have developed protocols that use human induced pluripotent stem cell (hiPSC)-derived neurons in a panel of assays to monitor neuronal health and performance. These assays include high content microscopy-based phenotypic evaluation of morphology, live cell monitoring of mitochondrial function and the use of multi-electrode array (MEA) assays to measure neuronal communication. Now routinely generated in a multi-well format are cultures of neurons, which recapitulate physiologically relevant synchronized bursting properties sensitive to shifts in excitation/inhibition balance. This greatly expands the possible uses of our platform. We will discuss use of these assays for compound screening and modeling of synaptic plasticity. Authors: Anne Bang, Sean Sherman, Sandy Hinckley, Steven Biesmans, Deborah Pre, Emily Pugach, and Michael Jackson.