Histopathological and behavioral improvement of murine mucopolysaccharidosis type VII by intracerebral transplantation of neural stem cells
Histopathological and behavioral improvement of murine mucopolysaccharidosis type VII by intracerebral transplantation of neural stem cells
复制标题
DOI：
10.1016/j.ymthe.2005.09.020
复制
发表时间：
2006-03-01
影响因子：
12.4
通讯作者：
Okuyama, T
中科院分区：
文献类型：
--
作者：
Fukuhara, Y;Li, XK;Okuyama, T
使用粘多糖沉积症VII型（MPS VII）小鼠模型探索神经干细胞移植治疗溶酶体贮积症中枢神经系统（CNS）病变的疗效。我们使用胚胎神经干细胞来源于胚胎小鼠纹状体和扩大在体外形成的神经球作为移植材料的来源。我们将神经球移植到新生MPS VII小鼠的侧脑室中，发现供体细胞在24小时内迁移到远远超出注射部位，其中一些可以到达嗅球。定量测量表明，在移植后24小时和3周，脑中的GUSB活性为正常活性的12.5%至42.3%和5.5%至6.3%。此外，组织学分析显示受体海马、皮质和室管膜中的溶酶体储存广泛减少。一项功能评估与新物体识别测试证实了行为模式的改善。这些结果表明，脑内移植神经干细胞是可行的治疗与溶酶体贮积症相关的CNS病变。
The therapeutic efficacy of neural stem cell transplantation for central nervous system (CNS) lesions in lysosomal storage disorders was explored using a murine model of mucopolysaccharidosis type VII (MPS VII). We used fetal neural stem cells derived from embryonic mouse striata and expanded in vitro by neurosphere formation as the source of graft materials. We transplanted neurospheres into the lateral ventricles of newborn MPS VII mice and found that donor cells migrated far beyond the site of injection within 24 h, and some of them could reach the olfactory bulb. A quantitative measurement indicated that the GUSB activity in the brain was 12.5 to 42.3% and 5.5 to 6.3% of normal activity at 24 h and 3 weeks after transplantation. In addition, histological analysis revealed a widespread decrease in lysosomal storage in the recipient's hippocampus, cortex, and ependyma. A functional assessment with novel-object recognition tests confirmed improvements in behavioral patterns. These results suggest that intracerebral transplantation of neural stem cells is feasible for treatment of CNS lesions associated with lysosomal storage disorders.