神经嵴细胞及其潜在的治疗应用

K. Shevchenko
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摘要

神经嵴(Neural crest, NC)是一群细胞,形成于非神经外胚层和神经管之间的交叉处。神经嵴祖细胞是多能的,具有广泛迁移和自我更新的能力。从颅面骨组织到周围神经系统的组成部分,它们可以分化为各种类型的细胞。不同阶段表达的信号分子和转录因子的影响调节着NC的发育。神经嵴细胞(neural crest cells, NCC)的诱导、规范、迁移和分化过程由基因调控网络决定。本文的目的是比较从胚胎、胎儿和成人组织中获得的NCC的特征;从胚胎干细胞、诱导多能干细胞、皮肤成纤维细胞中获得NCC的实验策略比较不同类型细胞在临床治疗中的应用潜力。胚胎干NCC根据其最初迁移的区域可分为干、颅、心、咽周和迷走神经。成熟干NCC可从背根神经节、红骨髓、毛囊、皮肤、肠、颈动脉体、心脏、角膜、虹膜、牙髓、硬腭和口腔黏膜中获得。基因突变可能导致NC发育调控失败,从而导致许多先天性人类疾病,如心血管缺陷、颅面异常和肠神经节病,统称为神经嵴病变。成体组织、胚胎干细胞和诱导多能干细胞多能干细胞的鉴定和分离是再生医学的重要来源。
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Neural crest cells and their potential therapeutic applications
Neural crest (NC) is a population of cells, formed at the intersection between non-neural ectoderm and neural tube. Neural crest progenitors are multipotent, have capacity to extensive migration and self-renewal. They can be differentiated into various cells types from craniofacial skeletal tissues to components of peripheral nervous system. Influence of signaling molecules and transcription factors, which are expressed at the different stages regulate development of NC. The regulatory network of genes determines the processes of induction, specification, migration and differentiation of neural crest cells (NCC). The purpose of this article is to compare the characteristics of NCC, obtained from tissues of the embryo, fetus and adult; experimental strategies for obtaining NCC from embryonic stem cells, induced pluripotent stem cells, skin fibroblasts; comparison of the potential of different cell types for therapeutic use in a clinical setting. Embryonic stem NCC are differentiated to the trunk, cranial, cardiac, circumpharyngeal and vagal according to the area of their initial migration. Mature stem NCC can be obtained from the dorsal root ganglia, red bone marrow, hair follicle, skin, intestines, carotid body, heart, cornea, iris, dental pulp, hard palate and oral mucosa. Genetic mutations may lead to failure of regulation of NC development, which leads to many congenital human diseases such as cardiovascular defects, craniofacial abnormalities and intestinal aganglionosis, collectively known as neurocristopathies. The identification and isolation of multipotent stem NCC derived from adult tissues, embryonic stem cells, and induced pluripotent stem cells are promising source for regenerative medicine.
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