Human progenitor cells isolated from the developing cortex undergo decreased neurogenesis and eventual senescence following expansion in vitro
Human progenitor cells isolated from the developing cortex undergo decreased neurogenesis and eventual senescence following expansion in vitro
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DOI：
10.1016/j.yexcr.2006.03.012
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发表时间：
2006-07-01
影响因子：
3.7
通讯作者：
Svendsen, Clive N.
中科院分区：
文献类型：
--
作者：
Wright, Lynda S.;Prowse, Karen R.;Svendsen, Clive N.
从人脑中分离出真正的自我更新干细胞作为神经组织的可靠来源将引起极大的兴趣。在这里，我们报告说，人胎儿皮质细胞生长在表皮生长因子表达低水平的端粒酶和端粒在这些文化缩短随着时间的推移，导致生长停滞后30周。补充白血病抑制因子（LIF）后，生长速率和端粒酶表达增加。这是最好的证明后，细胞周期同步化和染色端粒酶使用免疫细胞化学。这种活性的增加导致端粒在体外维持约7 kb超过60周。然而，所有的文化表现出缺乏少突胶质细胞的生产，随着时间的推移，减少神经发生，并经历了复制衰老与p21的表达增加70周前在体外。因此，在我们的培养条件下，这些细胞不是稳定的、多能的、表达端粒酶的自我更新干细胞。它们可以更准确地描述为具有有限寿命和双能潜能（神经元/星形胶质细胞）的人神经祖细胞（hNPC）。有趣的是，hNPC遵循增殖、神经元产生和生长停滞的过程，类似于在人类皮层的扩展和发育期间所看到的，从而提供了可能的模型神经系统。此外，由于它们的高扩增潜力和缺乏致瘤性，这些细胞仍然是用于临床移植的独特且安全的组织来源。(c)2006年爱思唯尔公司All rights reserved.
Isolation of a true self-renewing stem cell from the human brain would be of great interest as a reliable source of neural tissue. Here, we report that human fetal cortical cells grown in epidermal growth factor expressed low levels of telomerase and telomeres in these cultures shortened over time leading to growth arrest after 30 weeks. Following leukemia inhibitory factor (LIF) supplementation, growth rates and telomerase expression increased. This was best demonstrated following cell cycle synchronization and staining for telomerase using immunocytochemistry. This increase in activity resulted in the maintenance of telomeres at approximately 7 kb for more than 60 weeks in vitro. However, all cultures displayed a lack of oligodendrotye production, decreases in neurogenesis over time and underwent replicative senescence associated with increased expression of p21 before 70 weeks in vitro. Thus, under our culture conditions, these cells are not stable, multipotent, telomerase expressing self-renewing stem cells. They may be more accurately described as human neural progenitor cells (hNPC) with limited lifespan and bi-potent potential (neurons/astrocytes). Interestingly, hNPC follow a course of proliferation, neuronal production and growth arrest similar to that seen during expansion and development of the human cortex, thus providing a possible model neural system. Furthermore, due to their high expansion potential and lack of tumorogenicity, these cells remain a unique and safe source of tissue for clinical transplantation. (c) 2006 Elsevier Inc. All rights reserved.