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首页> 外文学位 >Functional maturation of postmitotic neurons from human embryonic stem cell-derived neuroepithelium.
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Functional maturation of postmitotic neurons from human embryonic stem cell-derived neuroepithelium.

机译：来自人类胚胎干细胞的神经上皮的有丝分裂后神经元的功能成熟。

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摘要

The successful differentiation of neurons from human embryonic stem (hES) cells has offered potentially new therapeutic transplant material to treat a variety of neurological diseases. Although great progress has been made in creating specific neuronal subtypes required to treat different diseases, methods to create safe and effective transplantable neuronal cells have not been carefully studied. In this thesis, I have attempted to understand how the proliferation of hES-derived neuronal progenitors, the most likely stage of cells for transplantation, is controlled. I also assessed the ability of astrocytes and their secreted factors to promote the functional maturation and integration of hES derived neurons into neuronal circuits, an essential property for functional neural transplantation. Specifically, I present evidence that hES-derived neuronal progenitors undergo spontaneous Ca2+ transients that can be blocked by inhibitors of transient receptor potential (Trp) channels, which also inhibit proliferation within the progenitor pool. Furthermore, I have demonstrated that newly born post-mitotic neurons depend on members of the TrpC family for proper neurite extension. I have demonstrated that the temporal pattern of physiologic maturation of hES derived neurons recapitulates that which occurs during human development and that the onset of synaptic activity within these cultures is modified by astrocytes. This work represents the first systematic analysis of hES derived neuronal progenitor proliferation and of the functional maturation of hES-derived neurons. Information gained from this study will provide a foundation for studying the functions of human neurons as well as designing safe functional neural transplants in humans.
机译：神经元从人类胚胎干细胞（hES）的成功分化为治疗各种神经系统疾病提供了潜在的新型治疗性移植材料。尽管在创建治疗不同疾病所需的特定神经元亚型方面已取得了巨大进展，但尚未仔细研究创建安全有效的可移植神经元细胞的方法。在本文中，我试图了解如何控制hES衍生的神经元祖细胞（最可能用于移植的细胞阶段）的增殖。我还评估了星形胶质细胞及其分泌因子促进功能成熟和将hES衍生神经元整合到神经元回路中的能力，这是功能性神经移植的基本特性。具体而言，我提供的证据表明，源自hES的神经元祖细胞会发生自发的Ca2 +瞬变，而瞬态受体电势（Trp）通道的抑制剂可能会阻断Ca2 +的瞬变，这也会抑制祖细胞内的增殖。此外，我已经证明新生的有丝分裂后神经元依赖于TrpC家族的成员进行适当的神经突延伸。我已经证明，hES衍生的神经元的生理成熟的时间模式可以概括人类发展过程中发生的现象，并且这些培养物中突触活性的开始被星形胶质细胞修饰。这项工作代表首次系统分析hES衍生的神经元祖细胞增殖和hES衍生的神经元功能成熟。从这项研究中获得的信息将为研究人类神经元的功能以及在人类中设计安全的功能性神经移植提供基础。

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  • 作者

    Johnson, M. Austin.;

  • 作者单位

    The University of Wisconsin - Madison.;

  • 授予单位 The University of Wisconsin - Madison.;
  • 学科 Biology Neuroscience.
  • 学位 Ph.D.
  • 年度 2008
  • 页码 199 p.
  • 总页数 199
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经科学;
  • 关键词

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