Walczak P, Chen N, Hudson J E, Willing A E, Garbuzova-Davis S N, Song S, Sanberg P R, Sanchez-Ramos J, Bickford P C, Zigova T
Center of Excellence for Aging and Brain Repair, Department of Neurosurgery, University of South Florida College of Medicine, Tampa, Florida 33612, USA.
J Neurosci Res. 2004 Apr 15;76(2):244-54. doi: 10.1002/jnr.20042.
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 CD 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.
造血祖细胞是一类细胞，在具有挑战性的实验条件下，它们会呈现出与其原始中胚层起源相差甚远的异常表型特性。如先前报道，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，在免疫细胞化学方面以及在某些情况下在形态学上，可表现出类似于神经源性细胞的神经特征。本研究探讨了造血来源的细胞如何响应成年和老年（6个月和16个月大）大鼠脑室下区（SVZ）的神经源性信号。将HUCB细胞的单核部分移植到免疫抑制（单剂量环孢素或三联药物治疗）动物的SVZ中。三联抑制模式使我们能够保护脑内移植的人类细胞，并进一步探究其表型和迁移特性。植入后一周，许多存活的HUCB细胞位于SVZ和吻侧迁移流（RMS）的垂直支内。HUCB细胞的迁移仅局限于通向嗅球的路径。在较年轻的动物中，移植细胞几乎穿过垂直支的一半，而在较年长的动物中，迁移则不太明显。较年轻动物中的总体细胞存活率高于较年长动物。表面CD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，都保留了它们的造血特性。使用人特异性抗体（抗人细胞核或线粒体）鉴定出的少数细胞表达了巢蛋白和双皮质素，这是内源性神经祖细胞的标志物。因此，人们认为，即使在老年动物中，神经源性SVZ的环境也能够支持HUCB来源细胞的存活、“神经化”和迁移特性。
