Physiological maturation and drug responses of human induced pluripotent stem cell-derived cortical neuronal networks in long-term culture.
Physiological maturation and drug responses of human induced pluripotent stem cell-derived cortical neuronal networks in long-term culture.
复制标题
DOI：
10.1038/srep26181
复制
发表时间：
2016-05-18
影响因子：
4.6
通讯作者：
Suzuki I
中科院分区：
文献类型：
--
作者：
Odawara A;Katoh H;Matsuda N;Suzuki I
人诱导多能干细胞（hiPSC）衍生神经元的功能网络是一个潜在的强大的体外模型，用于评估疾病机制和药物反应。然而，单个神经元和网络的完全功能成熟所需的培养时间是不确定的。我们研究了发展的自发电生理活动和药理学反应超过1年的文化，使用多电极阵列（MEA）。自发放电、诱发反应和多巴胺能和GABA能受体拮抗剂/激动剂对活动的调节的完全成熟需要20-30周。在这个阶段，神经网络也表现出癫痫样同步爆发放电（SBF），以响应使用临床抗癫痫药物的促惊厥剂和SBF抑制。我们的研究结果揭示了从hiPSC衍生的神经元网络在体外进行长期MEA测量用于机制分析和药物筛选的可行性。然而，电生理学和药理学特性的发展变化表明有必要对培养和评价程序进行国际标准化。
The functional network of human induced pluripotent stem cell (hiPSC)-derived neurons is a potentially powerful in vitro model for evaluating disease mechanisms and drug responses. However, the culture time required for the full functional maturation of individual neurons and networks is uncertain. We investigated the development of spontaneous electrophysiological activity and pharmacological responses for over 1 year in culture using multi-electrode arrays (MEAs). The complete maturation of spontaneous firing, evoked responses, and modulation of activity by glutamatergic and GABAergic receptor antagonists/agonists required 20–30 weeks. At this stage, neural networks also demonstrated epileptiform synchronized burst firing (SBF) in response to pro-convulsants and SBF suppression using clinical anti-epilepsy drugs. Our results reveal the feasibility of long-term MEA measurements from hiPSC-derived neuronal networks in vitro for mechanistic analyses and drug screening. However, developmental changes in electrophysiological and pharmacological properties indicate the necessity for the international standardization of culture and evaluation procedures.