ERI: Mechanistic understanding of neural stem cell paracrine activity and extracellular vesicle secretion directed by wireless electrical stimulation

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Neural stem cells (NSCs) can give rise to all types of cells found in the nervous system. They have considerable therapeutic potential to treat central nervous system disease and trauma. NSCs also generate extracellular vesicles (EVs). The EVs transport bioactive molecules that prompt cellular-level responses. It has been observed that electrical stimulation can modify the rate of EV formation. This project will apply experimental and machine learning strategies to understand the cellular mechanisms that undergird those responses. A wireless stimulation array to direct cellular and tissue responses remotely will be developed utilizing these insights. Workforce development will be achieved through teaching modules and training and research opportunities offered to graduate and undergraduate students.Using EVs instead of transplanting NSCs has certain advantages. Immune system rejection is lower. EVs also cross membrane barriers more easily. The challenges of using EVs are significant. They must contain a therapeutic level of biomolecules, and they must be manufactured in sufficient quantities to support clinically relevant dosages. The objective of this proposal is to achieve a comprehensive understanding of the mechanisms of NSC paracrine activity and EVs secretion directed by wireless electrical stimulation to biomanufacture therapeutics for CNS related problems. The first objective will focus on developing mechanistic understanding of wireless electrical stimulation-directed NSCs’ EVs secretion and their therapeutic content. The second objective is to design a wireless array system for high throughput NSCs stimulation to enable EVs biomanufacturing. High throughput stimulation and adaptive design of experiment using statistical and machine learning tools will be employed to generate scientific insights.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.