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Embryonic Stem Cell-Derived Neurons are a Novel, Highly Sensitive Tissue Culture Platform for Botulinum Research

机译：胚胎干细胞衍生神经元是一种用于肉毒杆菌研究的新型，高度敏感的组织培养平台

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There are no pharmacological treatments to rescue botulinum neurotoxin (BoNT)-mediated paralysis of neuromuscular signaling. In part, this failure can be attributed to the lack of a cell culture model system that is neuron-based, allowing detailed elucidation of the mechanisms underlying BoNT pathogenesis, yet still compatible with modern cellular and molecular approaches. We have developed a method to derive highly enriched, glutamatergic neurons from suspension-cultured murine embryonic stem (ES) cells. Hypothesizing that ES cell-derived neurons (ESNs) might comprise a novel platform to investigate the neurotoxicology of BoNTs, we evaluated the susceptibility of ESNs to BoNT/A and BoNT/E using molecular and functional assays. ESNs express neuron-specific proteins, develop synapses and release glutamate in a calcium-dependent manner under depolarizing conditions. They express the BoNT substrate SNARE proteins SNAP25, VAMP2 and syntaxin, and treatment with BoNT/A and BoNT/E holotoxin results in proteolysis of SNAP25 within 24 h with EC50s of 0.81 and 68.6 pM, respectively. Intoxication with BoNT/A results in the functional inhibition of potassium-induced, calcium- dependent glutamate release. ESNs remain viable and susceptible to intoxication for up to 90 days after plating, enabling longitudinal screens exploring toxin- specific mechanisms underlying persistence of synaptic blockade. The evidence suggests that derived neurons are a novel, biologically relevant model system that combines the verisimilitude of primary neurons with the genetic tractability and scalable expansion of a continuous cell line, and thus should significantly accelerate BoNT research and drug discovery while dramatically decreasing animal use.

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McNutt, P.; Celver, J.; Hamilton, T.; Mesngon, M.;
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年度 2011
页码 1-7
总页数 7
原文格式 PDF
正文语种 eng
中图分类工业技术;
关键词
Stem cells ; Nerve cells ; Clostridium botulinum ; Tissue culture ; Sensitivity ; Reprints ; Embryos;

机译：干细胞;神经细胞;肉毒梭菌;组织培养;敏感性;重印;胚胎;

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1. Embryonic stem cell-derived neurons are a novel, highly sensitive tissue culture platform for botulinum research. [J] . McNutt P, Celver J, Hamilton T, Biochemical and Biophysical Research Communications . 2011,第1期

机译：胚胎干细胞衍生的神经元是用于肉毒杆菌研究的新型，高度敏感的组织培养平台。
2. Embryonic stem cell-derived motoneurons provide a highly sensitive cell culture model for botulinum neurotoxin studies, with implications for high-throughput drug discovery [J] . Kiris E., Nuss J.E., Burnett J.C., Stem cell research . 2011,第3期

机译：胚胎干细胞衍生的运动神经元为肉毒杆菌神经毒素研究提供了高度敏感的细胞培养模型，对高通量药物发现具有重要意义
3. Embryonic stem cell-derived motoneurons provide a highly sensitive cell culture model for botulinum neurotoxin studies, with implications for high-throughput drug discovery - ScienceDirect [J] . Erkan Kiris, Jonathan E. Nuss, James C. Burnett, Stem cell research . 2011,第3期

机译：胚胎干细胞衍生的运动神经元为肉毒杆菌神经毒素研究提供了高度敏感的细胞培养模型，对高通量药物发现具有影响-ScienceDirect
4. Bidirectional synaptic connection between primary and stem cell-derived neurons in co-culture device [C] . Shimba, Kenta, Saito, Atsushi, Takeuchi, Akimasa, Annual Conference of Japanese Society for Medical and Biological Engineering;Annual International Conference of the IEEE Engineering in Medicine and Biology Society . 2013

机译：共培养装置中原代和干细胞源性神经元之间的双向突触连接
5. Process Extension from Embryonic Stem Cell-Derived Motor Neurons through Synthetic Extracellular Matrix Mimics. [D] . McKinnon, Daniel Devaud. 2014

机译：通过合成的细胞外基质模拟物，从胚胎干细胞衍生的运动神经元扩展过程。
6. Embryonic stem cell derived motoneurons provide a highly sensitive cell culture model for botulinum neurotoxin studies with implications for high-throughput drug discovery [O] . Erkan Kiris, Jonathan E. Nuss, James C. Burnett, -1

机译：胚胎干细胞衍生的运动神经元为肉毒杆菌神经毒素研究提供高度敏感的细胞培养模型具有对高通量药物发现的影响
7. Embryonic stem cell-derived motoneurons provide a highly sensitive cell culture model for botulinum neurotoxin studies, with implications for high-throughput drug discovery [O] . Kiris Erkan, Nuss Jonathan E., Burnett James C., 2011

机译：胚胎干细胞衍生的运动神经元为肉毒杆菌神经毒素研究提供了高度敏感的细胞培养模型，对高通量药物发现具有重要意义

Embryonic Stem Cell-Derived Neurons are a Novel, Highly Sensitive Tissue Culture Platform for Botulinum Research

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