Survival and differentiation of neural progenitor cells derived from embryonic stem cells and transplanted into ischemic brain
Survival and differentiation of neural progenitor cells derived from embryonic stem cells and transplanted into ischemic brain
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DOI：
10.3171/jns.2005.103.2.0304
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发表时间：
2005-08-01
影响因子：
4.1
通讯作者：
Hashimoto, N
中科院分区：
文献类型：
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作者：
Takagi, Y;Nishimura, M;Hashimoto, N
Object.包括胚胎干细胞（ESC）在内的细胞替代疗法可能是治疗中风损伤的一种新方法。本研究将来源于胚胎干细胞的神经前体细胞（neural progenitor cells，NPCs）移植到缺血脑组织中，观察其存活和分化情况。通过使用基质细胞衍生的诱导活性方法从ESCs产生多潜能NPC。这些细胞在体外可分化为神经元、神经胶质细胞和少突胶质细胞，从而揭示它们是神经干细胞。然后将NPC移植到缺血脑中。在2周postisemia，移植的细胞占18.8 - 2.5%的半球面积; 4周postisemia，26.5 +/- 4%的半球。移植后4周，绿色荧光蛋白（GFP）阳性的移植细胞显示出成熟的神经元形态学特征。作者还研究了分化标志物和各种神经递质的表达。移植细胞的神经元细胞核，β-微管蛋白-III，和胶质细胞酸性蛋白免疫阳性。在GFP阳性细胞中，33.3 +/- 11.5%为谷氨酸脱羧酶阳性，13.3 +/- 5.8%为谷氨酸，2.1 +/- 2.5%为酪氨酸羟化酶，1.8 +/- 2%为5-羟色胺，0.4 +/- 0.2%为胆碱乙酰转移酶。作者证实了移植到缺血脑中的ESC衍生的NPC的存活和分化。存活的移植细胞表达了几种神经标记物和神经递质。这些发现表明这些细胞可以在大脑中发挥作用。
Object. Cell replacement therapy including the use of embryonic stem cells (ESCs) may represent a novel treatment for damage from stroke. In this study, the authors transplanted neural progenitor cells (NPCs) derived from ESCs into ischemic brain and analyzed their survival and differentiation.Methods. Multipotential NPCs were generated from ESCs by using the stromal cell-derived inducing activity method. These cells could differentiate in vitro into neurons, glia, and oligodendrocytes, thus revealing them to be neural stem cells. The NPCs were then transplanted into ischemic brain. At 2 weeks postischemia, the transplanted cells occupied 18.8 2.5% of the hemispheric area; by 4 weeks postischemia, 26.5 +/- 4% of the hemisphere. At 4 weeks after transplantation, green fluorescent protein (GFP)-positive transplanted cells showed mature neuronal morphological features. The authors also investigated the expression of differentiation markers and various neurotransmitters. Transplanted cells were immunopositive for neuronal nuclei, beta-tubulin-III, and glial fibrillary acidic protein. Of the GFP-positive cells, 33.3 +/- 11.5% were positive for glutamate decarboxylase, 13.3 +/- 5.8% for glutamate, 2.1 +/- 2.5% for tyrosine hydroxylase, 1.8 +/- 2% for serotonin, and 0.4 +/- 0.2% for choline acetyltransferase.Conclusions. The authors confirmed the survival and differentiation of ESC-derived NPCs transplanted into the ischemic brain. Surviving transplanted cells expressed several neural markers and neurotransmitters. These findings indicate that these cells can function in the brain.