Do hematopoietic cells exposed to a neurogenic environment mimic properties of endogenous neural precursors?
Do hematopoietic cells exposed to a neurogenic environment mimic properties of endogenous neural precursors?
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DOI：
10.1002/jnr.20042
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发表时间：
2004-04-15
影响因子：
4.2
通讯作者：
Zigova, T
中科院分区：
文献类型：
--
作者：
Walczak, P;Chen, N;Zigova, T
造血祖细胞是在具有挑战性的实验条件下可以发展出不寻常的表型特性的细胞，与其原始的中胚层起源相距甚远。正如之前报道的，源自人脐带血（HUCB）或人骨髓（BM）的细胞在某些体内或体外条件下可以表现出与神经源细胞特征相似的神经特征，在免疫细胞化学上，在某些情况下也在形态学上。本研究探讨了造血源性细胞如何响应来自成年和老年（6 个月和 16 个月大）大鼠室下区 (SVZ) 的神经源性信号。将 HUCB 细胞的单核部分移植到免疫抑制（单一环孢素或三种药物治疗）动物的 SVZ 中。三重抑制范式使我们能够保护大脑内移植的人类细胞，并进一步探索它们的表型和迁移特性。植入一周后，许多存活的 HUCB 细胞位于 SVZ 和头侧迁移流 (RMS) 的垂直肢内。 HUCB 细胞的迁移仅限于通向嗅球的途径。在年轻的动物中，移植的细胞几乎在垂直肢体的一半处移动，而在年长的动物中，迁移不太明显。年轻动物的总体细胞存活率高于年老动物。表面 CID 抗原表达的免疫细胞化学显示，许多 HUCB 细胞，无论是培养的还是脑实质内的，都保留了其造血特性。通过使用人类特异性抗体（抗人类细胞核或线粒体）鉴定出一些细胞表达巢蛋白和双皮质素，这是内源性神经祖细胞的标记。因此，人们相信，即使在老年动物中，神经源性 SVZ 的环境也能够支持 HUCB 衍生细胞的生存、“神经化”和迁移特征。 (C) 2004 Wiley-Liss, Inc.
Hematopoietic progenitors are cells, which under challenging experimental conditions can develop unusual phenotypic properties, rather distant from their original mesodermal origin. As previously reported, cells derived from human umbilical cord blood (HUCB) or human bone marrow (BM) under certain in vivo or in vitro conditions can manifest neural features that resemble features of neural-derived cells, immunocytochemically and in some instances also morphologically. The present study explored how hematopoietic-derived cells would respond to neurogenic signals from the subventricular zone (SVZ) of adult and aged (6 and 16 months old) rats. The mononuclear fraction of HUCB cells was transplanted into the SVZ of immunosuppressed (single cyclosporin or three-drug treatment) animals. The triple-suppression paradigm allowed us to protect transplanted human cells within the brain and to explore further their phenotypic and migratory properties. One week after implantation, many surviving HUCB cells were located within the SVZ and the vertical limb of the rostral migratory stream (RMS). The migration of HUCB cells was restricted exclusively to the pathway leading to the olfactory bulb. In younger animals, grafted cells navigated almost halfway through the vertical limb, whereas, in the older animals, the migration was less pronounced. The overall cell survival was greater in younger animals than in older ones. Immunocytochemistry for surface CID antigen expression showed that many HUCB cells, either cultured or within the brain parenchyma, retained their hematopoietic identity. A few cells, identified by using human-specific antibodies (anti-human nuclei, or mitochondria) expressed nestin and doublecortin, markers of endogenous neural progenitors. Therefore, it is believed that the environment of the neurogenic SVZ, even in aged animals, was able to support survival, "neuralization," and migratory features of HUCB-derived cells. (C) 2004 Wiley-Liss, Inc.