3D neural spheroid models

National Center For Advancing Translational Sciences

Investigators

Abstract

The NCATS 3D Tissue Bioprinting Laboratory previously reported a process to assemble bran-region specific functional 3D neural spheroids using iPSC-derived neurons and astrocytes. These 3D neural spheroids displayed spontaneous synchronized neural activity which could be readily measured in high throughput screening (HTS) plate-based format using calcium fluorescence dyes. We demonstrated that the calcium signal in these neural spheroids depended on neuronal type composition and changed when disease mutations were introduced. We also showed that this neural spheroid platform was robust for HTS. In the last year, we have shown that we can include iPSC-derived microglia in these neural spheroid models to increase their physiological relevance to model neuroinflammation, which is a common mechanism underlaying many neurological diseases, including Parkinsons disease. We have also shown that these neural spheroids can be used to investigate infectivity by neurotropic viruses and have shown that many of these viruses affect neural activity and there are compounds that prevent the neurological effects without prevent viral replication. We are also using these neural spheroids to screen libraries of neurotoxic compounds to generate data that can be used to create in silico predictive models of neurotoxicity. In collaboration with Dr. Balaji Krishnan at UTMB, we are exploring the use of neural spheroids to test the effect of PLD1 inhibitors on Alzheimer's Disease neural spheroids and have uncovered a role of these inhibitors in calcium regulation and synapsis function.