iPSC modeling of rare pediatric disorders
iPSC modeling of rare pediatric disorders
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DOI：
10.1016/j.jneumeth.2019.108533
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发表时间：
2020-02-15
影响因子：
3
通讯作者：
Francis, Kevin R.
中科院分区：
文献类型：
--
作者：
Freel, Bethany A.;Sheets, Jordan N.;Francis, Kevin R.
由于许多因素，辨别潜在的病理机制和确定治疗策略以治疗受罕见神经系统疾病影响的个体已被证明具有挑战性。例如，与更常见的疾病相比，影响神经系统的罕见疾病本质上缺乏适当的患者样本可用性，而动物模型通常不能准确重现特定的疾病表型。这些挑战阻碍了研究，否则可能阐明疾病的起始和进展方面，导致最终确定潜在的治疗方法。诱导多能干细胞（iPSC）作为具有确定遗传学的人类细胞模型的建立为在受控环境中研究罕见疾病提供了独特的机会。iPSC模型使研究人员能够在日益复杂的系统中定义特定细胞类型和信号通路的突变效应。在罕见疾病中，影响神经发育和神经功能的儿科疾病突出了对基于iPSC的疾病建模的迫切需要，这是由于与收集人类神经组织相关的固有困难和哺乳动物神经系统的复杂性。因此，罕见的神经发育障碍是利用基于iPSC的体外研究的理想候选者。在这篇综述中，我们讨论了iPSC领域在神经发育研究中的实用性和局限性，以及推测iPSC在罕见疾病中的未来应用和未满足的用途。
Discerning the underlying pathological mechanisms and the identification of therapeutic strategies to treat individuals affected with rare neurological diseases has proven challenging due to a host of factors. For instance, rare diseases affecting the nervous system are inherently lacking in appropriate patient sample availability compared to more common diseases, while animal models often do not accurately recapitulate specific disease phenotypes. These challenges impede research that may otherwise illuminate aspects of disease initiation and progression, leading to the ultimate identification of potential therapeutics. The establishment of induced pluripotent stem cells (iPSCs) as a human cellular model with defined genetics has provided the unique opportunity to study rare diseases within a controlled environment. iPSC models enable researchers to define mutational effects on specific cell types and signaling pathways within increasingly complex systems. Among rare diseases, pediatric diseases affecting neurodevelopment and neurological function highlight the critical need for iPSC-based disease modeling due to the inherent difficulty associated with collecting human neural tissue and the complexity of the mammalian nervous system. Rare neurodevelopmental disorders are therefore ideal candidates for utilization of iPSC-based in vitro studies. In this review, we address both the state of the iPSC field in the context of their utility and limitations for neurodevelopmental studies, as well as speculating about the future applications and unmet uses for iPSCs in rare diseases.