(1344-A) Microglia integrated 3D neural spheroids for disease modeling and therapeutic development
Monday, February 5, 2024
12:00 PM – 1:00 PM EST
Location: Exhibit Halls AB
Abstract: Microglia, the immune cells in the brain, regulate neuroinflammation which can contribute to the progression of neurodegenerative diseases such as Parkinson’s (PD) and Alzheimer’s disease (AD). Despite accumulating evidence pointing towards the involvement of microglia in PD and AD, there is a critical need for physiologically relevant neural models that recapitulate microglial contributions to neuroinflammation and neurodegenerative disease states for both translational studies and therapeutics discovery and development. We have recently described a high throughput screening (HTS) assay platform of functional brain region-specific neural spheroids models assembled by a scaffold-free aggregation process of human-induced pluripotent stem cells (hiPSCs) derived neurons and astrocytes. These brain region-specific neural spheroids display distinct neuronal type-specific calcium oscillation patterns sensitive to drug treatments making them suitable as functional assays for drug screening. To expand the pathological relevance and clinical predictability of these functional neural spheroid models for AD and PD, we have now developed modified protocols to integrate hiPSC-derived microglia into neural spheroids. The aims of the study is to (1) optimized conditions for tri-culture (neurons, astrocytes and microglia) neural spheroids with network activity, as measured by calcium oscillations; (2) characterization of the morphological and functional activity of the microglia cells throughout the culturing period, in both healthy and disease neural spheroids; and (3) assessment the modulation of inflammatory responses of microglia-containing spheroids with a focused library of compounds including anti-inflammatory agents. The results from this study will provide therapeutic validation of the functional 3D neural spheroid assay platform for neurodegenerative diseases associated with neuroinflammation.