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

神经干细胞（NSCs）可以产生神经系统中所有类型的细胞。它们在治疗中枢神经系统疾病和创伤方面具有相当大的治疗潜力。NSCs也产生细胞外囊泡（EVs）。电动汽车运输生物活性分子，促进细胞水平的反应。已经观察到电刺激可以改变EV形成的速度。该项目将应用实验和机器学习策略来理解这些反应背后的细胞机制。利用这些见解，将开发一种远程指导细胞和组织反应的无线刺激阵列。劳动力发展将通过为研究生和本科生提供的教学模块和培训和研究机会来实现。使用电动汽车代替移植NSCs具有一定的优势。免疫系统排斥更低。电动汽车也更容易跨越膜屏障。使用电动汽车的挑战是巨大的。它们必须含有治疗水平的生物分子，并且必须以足够的数量生产以支持临床相关剂量。本提案的目的是全面了解无线电刺激对中枢神经系统相关问题生物制造治疗的NSC旁分泌活性和ev分泌机制。第一个目标将集中于发展对无线电刺激引导的NSCs的ev分泌及其治疗内容的机制理解。第二个目标是设计一种用于高通量NSCs刺激的无线阵列系统，以实现电动汽车的生物制造。使用统计和机器学习工具的高通量刺激和自适应实验设计将被用来产生科学见解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.