Neuronal Transplantation for Alzheimer's Disease and Prospects for Generating Exogenic Neurons as a Source of Cells for Implantation.
Neuronal Transplantation for Alzheimer's Disease and Prospects for Generating Exogenic Neurons as a Source of Cells for Implantation.
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DOI：
10.1177/09636897231164712
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发表时间：
2023-01
影响因子：
3.3
通讯作者：
Low, Walter C. C.
中科院分区：
文献类型：
--
作者：
Strell, Phoebe;Johnson, Sether T. T.;Carchi, Chris;Low, Walter C. C.
关键词：
阿尔茨海默病（AD）是一种具有破坏性的神经退行性疾病，治疗选择有限。先前已经在AD动物模型中探索了健康外源性神经元的细胞移植以替换和恢复神经元细胞功能，然而这些移植方法中的大多数已经利用原代细胞培养物或供体移植物。囊胚互补提供了一种产生可再生外源神经元的新方法。这些来源于干细胞的外源性神经元将在宿主内的诱导线索的体内环境下发育，从而重现神经元特异性特征和生理学。AD影响许多不同的细胞类型，包括海马神经元和边缘投射神经元、胆碱能基底核和内侧隔神经元、去甲肾上腺素能蓝斑神经元、肾上腺素能中缝神经元以及边缘和皮质中间神经元。胚泡互补可以通过消除重要的细胞类型和脑区域特异性发育基因来适应于产生这些受AD病理学折磨的特定神经元细胞。这篇综述讨论了神经元移植的现状，以取代特定的神经细胞类型受AD，发育生物学，以确定候选基因敲除在胚胎中创建壁龛，通过胚泡互补产生外源性神经元。
Alzheimer’s disease (AD) is a devastating neurodegenerative disease with limited therapeutic options. Cellular transplantation of healthy exogenic neurons to replace and restore neuronal cell function has previously been explored in AD animal models, yet most of these transplantation methods have utilized primary cell cultures or donor grafts. Blastocyst complementation offers a novel approach to generate a renewable exogenic source of neurons. These exogenic neurons derived from stem cells would develop with the in vivo context of the inductive cues within a host, thus recapitulating the neuron-specific characteristics and physiology. AD affects many different cell types including hippocampal neurons and limbic projection neurons, cholinergic nucleus basis and medial septal neurons, noradrenergic locus coeruleus neurons, serotonergic raphe neurons, and limbic and cortical interneurons. Blastocyst complementation can be adapted to generate these specific neuronal cells afflicted by AD pathology, by ablating important cell type and brain region–specific developmental genes. This review discusses the current state of neuronal transplantation to replace specific neural cell types affected by AD, and the developmental biology to identify candidate genes for knockout in embryos for creating niches to generate exogenic neurons via blastocyst complementation.
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