Survival, migration and neuronal differentiation of human fetal striatal and cortical neural stem cells grafted in stroke-damaged rat striatum
Survival, migration and neuronal differentiation of human fetal striatal and cortical neural stem cells grafted in stroke-damaged rat striatum
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DOI：
10.1111/j.1460-9568.2007.05702.x
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发表时间：
2007-08-01
影响因子：
3.4
通讯作者：
Kokaia, Zaal
中科院分区：
文献类型：
--
作者：
Darsalia, Vladimer;Kallur, Therese;Kokaia, Zaal
中风是一种神经退行性疾病，是成年人残疾的主要原因。支持中风患者有效康复的治疗方法缺乏。一些研究已经证明了移植的神经干细胞（NSC）能够部分改善中风动物受损的神经功能。最近，我们报道，从人胎儿纹状体和皮层神经干细胞在体外表现出区域特异性分化，但存活，迁移和形成神经元的新生大鼠纹状体内移植后，在相似的程度。在这里，我们将相同的细胞移植到中风受损的成年大鼠纹状体中。两种类型的神经干细胞在移植后1个月表现出相似的稳健存活率（30%），并在整个受损的纹状体中迁移。纹状体神经干细胞迁移更远，占据纹状体更大的体积。在移植核心中，细胞未分化并表达巢蛋白，并且在较小程度上还表达GFAP、β III-微管蛋白、DCX和钙视黄蛋白（未成熟神经谱系的标志物）。使用增殖标记物（p-H3和Ki 67）的免疫细胞化学显示移植物中增殖细胞的含量非常低（< 1%）。移植核心外的人细胞分化，表现出成熟的神经元形态，并表达成熟的神经元标记物，如HuD，钙结合蛋白和小清蛋白。有趣的是，纹状体神经干细胞产生更多的小清蛋白（+）和钙结合蛋白（+）神经元。几乎没有移植的细胞分化成星形胶质细胞或少突胶质细胞。基于这些数据，人胎儿纹状体和皮质来源的神经干细胞可以被认为是潜在的安全和可行的移植，具有强大的神经源性潜力，进一步探索中风的动物模型。
Stroke is a neurodegenerative disorder and the leading cause of disability in adult humans. Treatments to support efficient recovery in stroke patients are lacking. Several studies have demonstrated the ability of grafted neural stem cells (NSCs) to partly improve impaired neurological functions in stroke-subjected animals. Recently, we reported that NSCs from human fetal striatum and cortex exhibit region-specific differentiation in vitro, but survive, migrate and form neurons to a similar extent after intrastriatal transplantation in newborn rats. Here, we have transplanted the same cells into the stroke-damaged striatum of adult rats. The two types of NSCs exhibited a similar robust survival (30%) at 1 month after transplantation, and migrated throughout the damaged striatum. Striatal NSCs migrated farther and occupied a larger volume of striatum. In the transplantation core, cells were undifferentiated and expressed nestin and, to a lesser extent, also GFAP, beta III-tubulin, DCX and calretinin, markers of immature neural lineage. Immunocytochemistry using markers of proliferation (p-H3 and Ki67) revealed a very low content of proliferating cells (< 1%) in the grafts. Human cells outside the transplantation core differentiated, exhibited mature neuronal morphology and expressed mature neuronal markers such as HuD, calbindin and parvalbumin. Interestingly, striatal NSCs generated a greater number of parvalbumin(+) and calbindin(+) neurons. Virtually none of the grafted cells differentiated into astrocytes or oligodendrocytes. Based on these data, human fetal striatum- and cortex-derived NSCs could be considered potentially safe and viable for transplantation, with strong neurogenic potential, for further exploration in animal models of stroke.