Long-term survival of human central nervous system progenitor cells transplanted into a rat model of Parkinson's disease
Long-term survival of human central nervous system progenitor cells transplanted into a rat model of Parkinson's disease
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DOI：
10.1006/exnr.1997.6634
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发表时间：
1997-11-01
影响因子：
5.3
通讯作者：
Dunnett, SB
中科院分区：
文献类型：
--
作者：
Svendsen, CN;Caldwell, MA;Dunnett, SB
从发育中的人类中枢神经系统（CNS）中分离出祖细胞，使用表皮生长因子和成纤维细胞生长因子-a的组合诱导分裂，然后移植到具有单侧多巴胺能损伤的成年大鼠的纹状体中。存活两周后发现大移植物，其中含有许多未分化细胞，其中一些正在迁移到宿主纹状体中。然而，到存活 20 周时，移植物核心处只剩下一小片细胞，而整个纹状体中都可以看到大量用人类特异性抗体标记的迁移星形胶质细胞。在一些动物的移植部位附近发现了完全分化的移植源性神经元，也用人类特异性抗体标记。许多这些神经元表达酪氨酸羟化酶，足以部分改善两只动物损伤引起的行为缺陷。这些结果表明，在培养物中维持增殖状态的人类中枢神经系统祖细胞群体在脑内移植后可以迁移并分化为神经元和星形胶质细胞。因此，这些细胞可能具有开发作为退行性疾病神经移植的替代组织来源的潜力。 (C) 1997 年学术出版社。
Progenitor cells were isolated from the developing human central nervous system (CNS), induced to divide using a combination of epidermal growth factor and fibroblast growth factor-a, and then transplanted into the striatum of adult rats with unilateral dopaminergic lesions. Large grafts were found at 2 weeks survival which contained many undifferentiated cells, some of which were migrating into the host striatum. However, by 20 weeks survival, only a thin strip of cells remained at the graft core while a large number of migrating astrocytes labeled with a human-specific antibody could be seen throughout the striatum. Fully differentiated graft-derived neurons, also labeled with a human-specific antibody, were seen close to the transplant site in some animals. A number of these neurons expressed tyrosine hydroxylase and were sufficient to partially ameliorate lesion-induced behavioral deficits in two animals. These results show that expanded populations of human CNS progenitor cells maintained in a proliferative state in culture can migrate and differentiate into both neurons and astrocytes following intracerebral grafting. As such these cells may have potential for development as an alternative source of tissue for neural transplantation in degenerative diseases. (C) 1997 Academic Press.