Cell-based Model for Electrical Stimulation Safety Studies

描述（申请人提供）：用于电刺激安全性研究的基于细胞的模型 提出了一种基于细胞的体外模型，以评估电刺激对中枢神经系统（CNS）细胞的影响。该模型将被用于建立可能的伤害和非伤害水平的刺激假体和治疗，采用电极长期植入中枢神经系统。该模型将最大限度地减少评估刺激方案安全性所需的动物数量，允许研究比仅用动物研究实际或成本效益更大范围的刺激参数，并将提供用于研究电刺激诱导的细胞损伤机制的受控环境。第一阶段的工作有三个目标：1）开发适合于用穿透和平面微电极进行刺激研究的三维细胞培养模型，2）开发测量电刺激对细胞功能、促炎反应和细胞活力的影响的技术，以及3）基于动物中的皮质内电极研究，将模型中的细胞反应与已知安全或有害的刺激方案相关联。在第二阶段，将通过并排比较模型结果和动物研究来验证模型，并研究刺激诱导的神经组织损伤的潜在机制。该计划是EIC实验室，布朗大学和亨廷顿医学研究所（HMRI）之间的合作努力。最初的商业化目标是为医疗器械公司提供测试服务，并向合同研究组织和研究机构销售测试系统。

DESCRIPTION (provided by applicant): Cell-based Model for Electrical Stimulation Safety Studies The development of an in vitro, cell-based model to evaluate the effects of electrical stimulation on central nervous system (CNS) cells is proposed. The model would be used to establish likely injurious and non-injurious levels of stimulation in prostheses and therapies that employ electrodes chronically implanted in the CNS. The model would minimize the number of animals needed to assess the safety of stimulation protocols, allow the investigation of a wider range of stimulation parameters than is practical or cost-effective solely with animal studies, and would provide a controlled environment for studying mechanisms of cell damage induced by electrical stimulation. The Phase I effort has three Aims: 1) to develop a three-dimensional cell culture model suitable for stimulation studies with penetrating and planar microelectrodes, 2) to develop techniques to measure the influence of electrical stimulation on cell function, pro-inflammatory response, and cell viability, and 3) to correlate cellular responses in the model to stimulation protocols known to be safe or injurious based on intracortical electrode studies in animals. In Phase II, the model would be validated by side-by-side comparisons of model results and animal studies, and potential mechanisms of stimulation-induced neural tissue damage investigated. The program is collaborative effort between EIC Laboratories, Brown University, and the Huntingdon Medical Research Institutes (HMRI). The initial commercialization objective for is to provide testing services to medical device companies and the sale of test systems to contract research organizations and research institutions.