Integration of Stem Cell-Derived Neurons with Multi-Electrode Array

Abstract

The prevalence of serious mental illnesses (SMI) in the US adult population, in- cluding bipolar disorder (BP), major depressive disorder (MDD), and schizophrenia (SCZ), is estimated at 4-6%. While the creation of in vitro models from human induced pluripotent stem cells (hiPSCs) has transformed disease modeling in such illnesses, further research is needed to optimize these models. This project utilizes the human embryonic stem cell (hESC) line H1 to investigate the electrophysiological activity of stem cell-derived cortical neurons using Multi- Electrode Arrays (MEA). By integrating micro-electrodes into cell well-plates, neu- ral activity can be non-destructively measured over several weeks with MEA. The objective is to optimize the integration of stem cell-derived neurons with MEA for monitoring electrophysiological activity, evaluating different cell densities, coatings, and culturing mediums. Comprising a pilot study followed by a more extensive investigation, this project compares metrics such as activity and electrode coverage across various culturing conditions to identify optimal parameters. The most promising condition entails a cell density of 50k cells per well, coated with both Poly-L-Ornithine (PLO) and Bi- olaminin 521 (LN521), and cultured in either Neural Maintenance Medium (NMM) or BrainPhys (BP).