Survival and Differentiation of Rat and Human Epidermal Growth Factor-Responsive Precursor Cells Following Grafting into the Lesioned Adult Central Nervous System
Survival and Differentiation of Rat and Human Epidermal Growth Factor-Responsive Precursor Cells Following Grafting into the Lesioned Adult Central Nervous System
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大鼠和人表皮生长因子反应性前体细胞移植到受损成人中枢神经系统后的存活和分化
DOI：
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发表时间：
1996
影响因子：
5.3
通讯作者：
Stephen B. Dunnett
中科院分区：
文献类型：
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作者：
Clive N. Svendsen;D. Clarke;A. E. Rosser;Stephen B. Dunnett
从发育中的中枢神经系统（CNS）中分离的表皮生长因子（EGF）响应性干细胞可以在培养中以指数方式扩增，同时保留分化成神经元和神经胶质的能力。因此，它们代表了用于神经移植的组织的可能来源，只要它们在移植到成人脑中后能够存活和成熟。在这项研究中，我们已经表明，从胚胎中脑或纹状体产生的纯化大鼠干细胞可以存活移植到患有鹅膏蕈氨酸或黑质纹状体多巴胺损伤的大鼠的纹状体中。然而，移植的干细胞不能作为典型的原代胚胎CNS组织移植物的大团块存活，而是形成仅含有少量存活细胞的薄移植物。有没有广泛的迁移移植的干细胞标记的lac-z基因或溴脱氧尿苷到周围的移植物的宿主区域，虽然在腹侧纹状体中看到少量的标记细胞距离植入部位。其中一些似乎分化成多巴胺神经元，特别是当发育中的中脑被用作产生干细胞的起始材料时。EGF反应性干细胞也可以从发育中的人类胚胎的中脑中分离出来，并在培养中扩增，但只有当胚胎的胎龄大于11周时才能大量生长。纯化的人中枢神经系统干细胞也被移植到免疫抑制的黑质纹状体病变的大鼠，并形成薄的移植物时，所看到的使用大鼠干细胞。然而，当人类中脑的原代培养物与EGF一起生长仅10天时，将干细胞和原代神经组织的混合物移植到多巴胺耗尽的纹状体中，形成了大型良好的移植物。这些细胞主要是未分化的小细胞，与一些分化良好的TH阳性神经元混合。这些结果表明，纯化的大鼠或人EGF反应性CNS干细胞群体在移植到成年纹状体时不会形成大的移植物团块或广泛迁移到周围宿主组织中。然而，体外生长条件的改变可能导致其体内存活的改善。
Epidermal Growth Factor (EGF)-responsive stem cells isolated from the developing central nervous system (CNS) can be expanded exponentially in culture while retaining the ability to differentiate into neurons and glia. As such, they represent a possible source of tissue for neural transplantation, providing they can survive and mature following grafting into the adult brain. In this study we have shown that purified rat stem cells generated from either the embryonic mesencephalon or the striatum can survive grafting into the striatum of rats with either ibotenic acid or nigrostriatal dopamine lesions. However, transplanted stem cells do not survive as a large mass typical of primary embryonic CNS tissue grafts, but in contrast form thin grafts containing only a small number of surviving cells. There was no extensive migration of transplanted stem cells labeled with either the lac-z gene or bromodeoxyuridine into the host region surrounding the graft, although a small number of labeled cells were seen in the ventral striatum some distance from the site of implantation. Some of these appeared to differentiate into dopamine neurons, particularly when the developing mesencephalon was used as the starting material for generating the stem cells. EGF-responsive stem cells could also be isolated from the mesencephalon of developing human embryos and expanded in culture, but only grew in large numbers when the gestational age of the embryo was greater than 11 weeks. Purified human CNS stem cells were also transplanted into immunosuppressed rats with nigrostriatal lesions and formed thin grafts similar to those seen when using rat stem cells. However, when primary cultures of human mesencephalon were grown with EGF for only 10 days and this mixture of stem cells and primary neural tissue was transplanted into the dopamine-depleted striatum, large well-formed grafts developed. These contained mostly small undifferentiated cells intermixed with a number of well-differentiated TH-positive neurons. These results show that purified populations of rat or human EGF-responsive CNS stem cells do not form large graft masses or migrate extensively into the surrounding host tissues when transplanted into the adult striatum. However, modifications of the growth conditions in vitro may lead to an improvement of their survival in vivo.