人类iPSC衍生的感觉神经元的表征及其使用多电极阵列的功能评估
Minami Hiranuma1, Yuichi Okuda2, Yuuka Fujii2
1REPROCELL, Yokohama, Japan. minami.hiranuma@gmail.com.
Scientific reports
|March 13, 2024
概括
人类诱导的多能干细胞衍生的感觉神经元为研究疼痛和开发新药的动物模型提供了稳定,可扩展的替代方案. 这些细胞在体外有效地模仿人类感官神经元的功能.
科学领域:
- 神经科学是一个神经科学.
- 干细胞生物学 干细胞生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 背部根腺 (DRG) 感觉神经元对于疼痛信号至关重要,但很难培养,动物模型中的数量很低.
- 现有的动物衍生模型在体外研究中存在跨物种差异和供应稳定性的挑战.
- 人类诱导多能干细胞 (hiPSC) 衍生的感觉神经元为这些局限性提供了潜在的解决方案.
研究的目的:
- 描述hiPSC衍生的感觉神经元作为一种可行的体外模型来进行感知研究.
- 研究这些hiPSC衍生神经元的功能性质,基因/蛋白质表达和药物反应.
- 评估它们在治疗疼痛相关疾病的药物发现中的有用性.
主要方法:
- 培养和特征化hiPSC衍生的感觉神经元.
- 研究了与感觉神经元相关的基因和蛋白质的表达.
- 使用多电极阵列 (MEA) 来分析神经元活动和药物反应.
主要成果:
- 由hiPSC衍生的感觉神经元表达了关键的感觉受体,机械受体和自身受体标志物,形成了一个异质的群体.
- 神经元对有害和非有害的刺激都有反应,显示出功能相关性.
- 特定药物抑制剂 (组胺抑制剂,ProTx-II,Nav1.7抑制剂) 不同地调节神经元刺激性和自发活动.
结论:
- 由hiPSC衍生的感觉神经元成功地复制了初级感觉神经元的关键特征.
- 这些细胞提供了一个稳定且可扩展的体外模型,克服了来自动物的DRG的局限性.
- 由hiPSC衍生的感觉神经元和MEA的组合是疼痛研究中临床前药物发现的有希望的平台.
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