Studies of neurospheres and diseased neurospheres on chip under magnetic field stimulation and drug treatment

磁场刺激和药物治疗下芯片上神经球和病变神经球的研究

• 批准号: 2024797
• 负责人: Long Que
• 金额: $ 39.09万
• 依托单位: Iowa State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2024797&HistoricalAwards=false
• 关键词: Studies; neurospheres; diseased; chip; under

In the United States, about one in five Americans above the age of 18 suffer from diagnosable neurological disorders with no cure insight. As such, new, safe, non-invasive methods for the treatment of brain disorders are critically needed. Non-invasive techniques including repetitive transcranial magnetic stimulation (TMS) and transcranial direct current stimulation have had some success. However, progress has been limited due to poor understanding of the interactions of magnetic fields with nervous tissue. The molecular/cellular mechanisms of nervous tissue under TMS are still lacking. Hence, investigation of effects of transient magnetic fields on adult neurogenesis, cell differentiation and plasticity of nervous tissue (neurospheres) is essential in developing new treatment procedures and achieving the use of TMS as a neuromodulation tool for treating neurological disorders. The educational goal of this project is to effectively integrate research with educational activities and to train both undergraduate and graduate students in interdisciplinary studies to produce next-generation bioengineers. The PIs will develop a new Vertically Integrated Program (VIP) based on this research proposal entitled: Targeting Neurodegenerative Diseases Using Bioengineering Approaches. The VIP will unite undergraduate education and faculty research in a team-based context. The overall educational goal is to help next-generation workforce development by training students to carry out research with sound technical background and allowing them to gain hands-on laboratory skills for their advanced careers. The long-term goal is to design an automatic technical platform to synthesize a variety of in vitro central nervous system disease models to mimic in vivo conditions as closely as possible. This will facilitate the studies of TMS effects and drug screening assays for neurodegenerative disorders.The goal of this proposal is to develop a chip-based microfluidics platform that facilitates the rapid formation of three-dimensional in vitro cell culture models of the central nervous system, which will permit the investigation of mechanisms of organ development, cellular interactions, disease model progression under magnetic field stimulation and drug treatments within defined microenvironments. Specifically, the proposed efforts include (1) the development of a chip consisting of microchamber arrays so that neurospheres including diseased neurospheres such as Alzheimer’s disease (AD) neurospheres can be fabricated in an efficient manner; and (2) the studies of the behavior of healthy neurospheres and AD neurospheres under transient magnetic stimulation (MS) and drug treatment using this chip. Major innovations of this proposed project can be summarized as the following: (1) Using this type of microfluidic chip, large-scale neurospheres with tunable and quantitative compositions can be synthesized rapidly and inexpensively, facilitating studies of different types of neurospheres; (2) Using a concentration gradient generator at the upper stream of this chip, a series of AD models (AD neurospheres) with known concentrations of amyloid-β and/or phosphorylated-tau can be readily fabricated; and (3) developing this chip will thus facilitate studies of the effects of both MS and drug treatment on AD models.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.

在美国，大约18岁以上的五分之一的美国人患有诊断性中性疾病，没有治疗见解。因此，需要新的，安全的，无创的方法来治疗脑疾病。非侵入性技术，包括重复的经颅磁刺激（TMS）和经颅直流刺激，取得了一些成功。但是，由于对磁场与神经组织的相互作用的了解不足，进展受到限制。 TMS下神经组织的分子/细胞机制仍然缺乏。因此，瞬态磁场对成人神经发生，神经组织细胞分化和可塑性的影响（神经球）对于开发新治疗程序以及实现TMS作为治疗神经系统疾病的神经调节工具至关重要。该项目的教育目标是有效地将研究与教育活动相结合，并在跨学科研究中培训本科和研究生，以生产下一代生物工程师。 PI将根据该研究建议制定一个新的垂直集成程序（VIP），标题为：使用生物工程方法靶向神经退行性疾病。 VIP将在基于团队的背景下将本科教育和教职员工研究单位。总体教育目标是通过培训学生以合理的技术背景进行研究来帮助下一代劳动力发展，并允许他们为自己的高级职业获得动手实验室技能。长期目标是设计一个自动技术平台，以合成各种体外中枢神经系统疾病模型，以模仿体内疾病。这将促进对TMS效应和药物筛查测定神经性疾病的研究。该建议的目的是开发基于芯片的微流体平台，该平台有助于促进中枢神经系统的三维体外细胞培养模型的快速形成，这将允许在细胞相互作用下，疾病的投资，疾病的投资，疾病的投资，疾病的投资机构，疾病的投资机构，疾病的投资机构，疾病的投资机制，疾病的机制，疾病的投资机构，疾病的投资机构，疾病的投资机构，疾病的投资机构，疾病的投资机构，疾病的投资机构，疾病的投资机构，疾病的投资机构，疾病的投资机构，疾病的投资机构，并允许在中枢神经系统中进行启动。微环境。具体而言，拟议的工作包括（1）由微培训阵列组成的芯片的开发，以便可以有效地制造包括解剖神经球（例如阿尔茨海默氏病（AD）神经球）的神经球。 （2）使用此芯片在瞬时磁刺激（MS）和药物处理下健康神经球和AD神经球的行为的研究。该提出的项目的主要创新可以总结为以下内容：（1）使用这种类型的微流体芯片，具有可调和定量组成的大型神经球，可以快速且便宜地合成，以支持对不同类型的神经圈的研究； （2）使用该芯片上流流的浓度梯度发生器，这是一系列具有已知浓度淀粉样蛋白β和/或磷酸化TAU的AD模型（AD神经球）； （3）因此，开发这种芯片将促进对MS和药物治疗对AD模型的影响的研究。该奖项反映了NSF的法定任务，并通过使用基金会的知识分子优点和更广泛的影响来审查标准，通过评估来诚实地支持支持。

项目成果

A Microfluidic Chip for Growth and Characterization of Adult Rat Hippocampal Progenitor Cell Neurospheroids

用于成年大鼠海马祖细胞神经球体生长和表征的微流控芯片

• DOI: 10.1109/jmems.2021.3134632
• 发表时间: 2022
• 期刊: Journal of Microelectromechanical Systems
• 影响因子: 2.7
• 作者: Yang, Renyuan;Fonder, Catherine;Sylvester, Talia;Peng, Stefan;Jiles, David;Sakaguchi, Donald S.;Que, Long
• 通讯作者: Que, Long

An integrated microfluidic chip for studying the effects of neurotransmitters on neurospheroids

用于研究神经递质对神经球影响的集成微流控芯片

• DOI: 10.1039/d2lc00755j
• 发表时间: 2023
• 期刊: Lab on a Chip
• 影响因子: 6.1
• 作者: Mao, Subin;Fonder, Catherine;Rubby, Md Fazlay;Phillips, Gregory J.;Sakaguchi, Donald S.;Que, Long
• 通讯作者: Que, Long

A Microchip For Studying the Effects of Dopamine and its Precursor On Neurospheroids

用于研究多巴胺及其前体对神经球体影响的微芯片

• DOI: 10.1109/mems51670.2022.9699585
• 发表时间: 2022
• 期刊: 2022 IEEE 35th International Conference on Micro Electro Mechanical Systems Conference (MEMS
• 作者: Mao, Subin;Fonder, Catherine;Rubby, Fazlay;Yang, Renyuan;Phillips, Gregory;Sakaguchi, Donald;Que, Long
• 通讯作者: Que, Long

On chip detection of glial cell-derived neurotrophic factor secreted from dopaminergic cells under magnetic stimulation

磁刺激下多巴胺能细胞分泌的胶质细胞源性神经营养因子的芯片检测

• DOI: 10.1016/j.bios.2021.113179
• 发表时间: 2021
• 期刊: Biosensors and Bioelectronics
• 影响因子: 12.6
• 作者: Yang, Renyuan;Boldrey, Joseph;Jiles, David;Schneider, Ian;Que, Long
• 通讯作者: Que, Long