Immature electrophysiological properties of human-induced pluripotent stem cell-derived neurons transplanted into the mouse cortex for 7 weeks

Immature electrophysiological properties of human-induced pluripotent stem cell-derived neurons transplanted into the mouse cortex for 7 weeks
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DOI:
10.1097/wnr.0000000000001178
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发表时间:
2019-02-06
期刊:
影响因子:
1.7
通讯作者:
Sasaki, Takuya
Sasaki, Takuya
中科院分区:
医学4区
文献类型:
--
作者:
Kayama, Tasuku;Okamoto, Kazuki;Sasaki, Takuya

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人诱导多能干细胞(hiPSC)来源的细胞移植已成为治疗脑部疾病的潜在临床方法。最近的动物疾病模型研究表明,hipsc来源的神经元移植到大脑,特别是黑质纹状体区,可以恢复退化的大脑功能。需要进一步的工作来测试hipsc衍生的神经元是否也能获得其他皮质区域的功能特性。本研究将hipsc衍生的神经球移植到成年小鼠海马和感觉皮层。大多数移植的hipsc来源的神经元在移植后7周同时表达Nestin和NeuN。来自脑切片的全细胞膜片钳记录显示,移植细胞在电流注射时没有动作电位,并且很少有小的内向电流,这表明hipsc来源的神经元在这些时间段内没有功能成熟。
The transplantation of human-induced pluripotent stem cell (hiPSC)-derived cells has emerged as a potential clinical approach for the treatment of brain diseases. Recent studies with animal disease models have shown that hiPSC-derived neurons transplanted into the brain, especially the nigrostriatal area, could restore degenerated brain functions. Further works are required to test whether hiPSC-derived neurons can also gain functional properties for other cortical areas. In this study, hiPSC-derived neurospheres were transplanted into the adult mouse hippocampus and sensory cortex. Most transplanted hiPSC-derived neurons expressed both Nestin and NeuN at 7 weeks after transplantation. Whole-cell patch-clamp recordings from brain slices indicated that transplanted cells showed no action potentials upon current injection and few small inward currents, indicating that hiPSC-derived neurons did not become functionally mature within these time periods.