Human neural stem/progenitor cells, expanded in long-term neurosphere culture, promote functional recovery after focal ischemia in Mongolian gerbils
Human neural stem/progenitor cells, expanded in long-term neurosphere culture, promote functional recovery after focal ischemia in Mongolian gerbils
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DOI：
10.1002/jnr.20246
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发表时间：
2004-10-15
影响因子：
4.2
通讯作者：
Mizusawa, H
中科院分区：
文献类型：
--
作者：
Ishibashi, S;Sakaguchi, M;Mizusawa, H
人神经干细胞（NSCs）的移植是治疗人类中风超急性期后神经功能障碍的一种有前景的潜在疗法，但是为了这种疗法，必须在长期培养中扩增大量的人NSCs。为了确定其对人类中风的可能治疗潜力，人类胎儿神经干/祖细胞（NSPCs）（即，神经球形成细胞）最初从一个人胎儿的前脑组织中分离，并在长期神经球培养（超过24周）中扩增，然后在局灶性缺血后4天异种移植到蒙古沙鼠脑中的损伤区域中。移植后4周内评估感觉运动和认知功能。NSPC移植动物的总梗死体积显著低于对照组。移植的NSPCs中约8%存活，主要在选择性神经元死亡的区域，并与神经元核抗体（NeuN）、微管相关蛋白（MAP-2）、胶质细胞酸性蛋白（GFAP）和抗2 '3'环核苷酸3 '-磷酸二酯酶（CNE 2）的抗体共染色。观察NSPCs源性神经元与宿主神经元之间的突触结构。此外，与对照组相比，在NSPC移植动物中清楚地观察到神经功能的逐渐改善。人NSPCs，即使是长期培养，也能显著改善蒙古沙鼠局灶性缺血后的神经功能，并保持其在梗死周围迁移、分化为成熟神经元和与宿主神经元回路形成突触的能力。这些结果表明，体外扩增的人神经球细胞是治疗中风的可移植材料的潜在来源。(C)2004 Wiley-Liss，Inc.
Transplantation of human neural stem cells (NSCs) is a promising potential therapy for neurologic dysfunctions after the hyperacute stage of stroke in humans, but large amounts of human NSCs must be expanded in long-term culture for such therapy. To determine their possible therapeutic potential for human stroke, human fetal neural stem/progenitor cells (NSPCs) (i.e., neurosphere-forming cells) were isolated originally from forebrain tissues of one human fetus, and expanded in long-term neurosphere culture (exceeding 24 weeks), then xenografted into the lesioned areas in the brains of Mongolian gerbils 4 days after focal ischemia. Sensorimotor and cognitive functions were evaluated during the 4 weeks after transplantation. The total infarction volume in the NSPC-grafted animals was significantly lower than that in controls. Approximately 8% of the grafted NSPCs survived, mainly in areas of selective neuronal death, and were costained with antibodies against neuronal nuclei antibody (NeuN), microtubule associated protein (MAP-2), glial fibrillary acidic protein (GFAP), and anti-2'3' cyclic nucleotide 3'-phosphodiesterase (CNPase). Synaptic structures between NSPCs-derived neurons and host neurons were observed. Furthermore, gradual improvement of neurologic functions was observed clearly in the NSPC-grafted animals, compared to that in controls. Human NSPCs, even from long-term culture, remarkably improved neurologic functions after focal ischemia in the Mongolian gerbil, and maintained their abilities to migrate around the infarction, differentiate into mature neurons, and form synapses with host neuronal circuits. These results indicate that in vitro-expanded human neurosphere cells are a potential source for transplantable material for treatment of stroke. (C) 2004 Wiley-Liss, Inc.