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[哺乳动物脑干细胞:体内和体外干细胞生物学]

[Stem cells of mammalian brain: biology of the stem cells in vivo and in vitro].

作者信息

Viktorov I V

出版信息

Izv Akad Nauk Ser Biol. 2001 Nov-Dec(6):646-55.

Abstract

Stem cells are totipotent cells of the blastocyst (embryonal stem cells) and multipotent germinative cells of ento-, ecto-, and mesoderm that give rise to all tissues during embryogenesis. The stem cells have high proliferation activity and an unlimited capacity for self-production by symmetrical mitosis. Asymmetrical mitosis of the stem cells generates daughter cells ("progenitor cells") with unlimited proliferation potential. During differentiation, the progenitor cells give rise to definitive somatic cells. The stem and progenitor cells are preserved in most tissues of adult organism and provide for the constant replacement of the cells after their physiological death and damage. At the end of last century, stem cells were found in the brain of the adult mouse and rat and later in the brain of other mammals including humans. The subependymal zone of the lateral ventricles is considered the site of stem cells localization; however, there are indications of stem cells origination from ependyma while the subependymal zone serves as a collector of the progenitor cells where these cells divide. The problem of the localization of stem cells in a mature brain has not yet been resolved and is actively discussed. The stem and progenitor cells, as well as neuro- and gliogenesis, are most explored in the hippocampus and olfactory bulb. The progenitor cells migrate to the olfactory bulb from the subependymal zone of the lateral ventricles via a rostral migratory stream formed by the astrocytes, and then they differentiate to neural and glial cells. In the hippocampus, the neurons are formed in the subgranular zone of dentate gyrus. The discovery of stem and progenitor cells in the mature brain and their subsequent investigation point to an ongoing neuro- and gliogenesis in all periventricular sections of the brain and spinal cord during the whole animal or human lifespan. These processes proved to be related to the functional condition of CNS, and the de novo formed neural and glial cells proved to be involved in certain brain functions. Stress inhibits the proliferation of the stem cells, while certain brain pathologies (ischemia, injury, or epilepsy) can promote their division. Isolating and cultivating in vitro the stem progenitor cells yeilded their long-living clones, revealed the factors of their directed differentiation, and demonstrated the application of the native and genetically modified stem cells for the intrabrain transplantation of the cell and gene therapy of certain experimental brain pathologies, which offers a promising application of the stem cells for CNS maladies treatment. The aim of this review is to introduce the readers to the state of foreign studies on the brain stem cells by the beginning of 2001.

摘要

干细胞是囊胚的全能细胞(胚胎干细胞)以及内胚层、外胚层和中胚层的多能生殖细胞,它们在胚胎发育过程中产生所有组织。干细胞具有高增殖活性,通过对称有丝分裂具有无限的自我复制能力。干细胞的不对称有丝分裂产生具有无限增殖潜能的子细胞(“祖细胞”)。在分化过程中,祖细胞产生终末体细胞。干细胞和祖细胞存在于成年生物体的大多数组织中,并在细胞生理性死亡和受损后不断进行细胞替换。上世纪末,在成年小鼠和大鼠的大脑中发现了干细胞,后来在包括人类在内的其他哺乳动物的大脑中也发现了干细胞。侧脑室的室管膜下区被认为是干细胞的定位部位;然而,有迹象表明干细胞起源于室管膜,而室管膜下区则是祖细胞的聚集部位,这些细胞在此处进行分裂。成熟大脑中干细胞的定位问题尚未解决,仍在积极讨论中。在海马体和嗅球中,对干细胞、祖细胞以及神经发生和胶质发生的研究最为深入。祖细胞从侧脑室的室管膜下区通过由星形胶质细胞形成的吻侧迁移流迁移到嗅球,然后分化为神经细胞和胶质细胞。在海马体中,神经元在齿状回的颗粒下区形成。成熟大脑中干细胞和祖细胞的发现以及随后的研究表明,在整个动物或人类生命周期中,大脑和脊髓的所有脑室周围区域都在持续进行神经发生和胶质发生。这些过程被证明与中枢神经系统的功能状态有关,新形成 的神经细胞和胶质细胞被证明参与某些脑功能。应激会抑制干细胞的增殖,而某些脑部疾病(缺血、损伤或癫痫)可促进其分裂。在体外分离和培养干细胞和祖细胞产生了它们的长寿克隆,揭示了它们定向分化的因素,并证明了天然和基因修饰的干细胞在某些实验性脑部疾病的细胞和基因治疗的脑内移植中的应用,这为干细胞治疗中枢神经系统疾病提供了有前景的应用。这篇综述的目的是向读者介绍截至2001年初国外关于脑干细胞的研究状况。

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