Human Umbilical Vein-Derived Dopaminergic-Like Cell Transplantation with Nerve Growth Factor Ameliorates Motor Dysfunction in a Rat Model of Parkinson's Disease
Human Umbilical Vein-Derived Dopaminergic-Like Cell Transplantation with Nerve Growth Factor Ameliorates Motor Dysfunction in a Rat Model of Parkinson's Disease
复制标题
人脐静脉源性多巴胺能样细胞移植与神经生长因子可改善帕金森病大鼠模型的运动功能障碍
DOI：
10.1007/s11064-010-0211-6
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发表时间：
2010-10-01
影响因子：
4.4
通讯作者：
Su, Dao-qing
中科院分区：
文献类型：
--
作者：
Li, Ming;Zhang, Shi-Zhong;Su, Dao-qing
间充质干细胞能够分化为多巴胺能样细胞，但目前还没有报道描述人脐静脉间充质干细胞（HUVMSC）诱导为多巴胺能样细胞。在本研究中，我们在体外诱导HUVMSCs成为神经干细胞样细胞构成的神经球，并进一步成为细胞轴承强大的形态，表型和功能的相似性与多巴胺能样细胞。这些源自HUVMSC的多巴胺能样细胞在移植到帕金森病（PD）大鼠模型的脑中后，在行为改善方面显示出部分治疗效果。据报道，神经生长因子可以改善移植细胞的局部微环境，因此我们进一步测试了多巴胺能样细胞移植与神经生长因子（NGF）给药在细胞移植部位的效果。结果表明，NGF能显著促进移植细胞在宿主脑内的存活，并提高局部脑组织中多巴胺能神经元的含量。行为学测试表明，与仅接受细胞移植的大鼠相比，给予多巴胺能样细胞移植后的PD大鼠的运动功能显著改善。这些结果表明，移植多巴胺能样细胞联合应用神经生长因子可能是帕金森病干细胞治疗的新策略。
Mesenchymal stem cells are capable of differentiating into dopaminergic-like cells, but currently no report has been available to describe the induction of human umbilical vein mesenchymal stem cells (HUVMSCs) into dopaminergic-like cells. In this study, we induced HUVMSCs in vitro into neurospheres constituted by neural stem-like cells, and further into cells bearing strong morphological, phenotypic and functional resemblances with dopaminergic-like cells. These HUVMSC-derived dopaminergic-like cells, after grafting into the brain of a rat model of Parkinson's disease (PD), showed a partial therapeutic effect in terms of the behavioral improvement. Nerve growth factor was reported to improve the local microenvironment of the grafted cells, and we therefore further tested the effect of dopaminergic-like cell grafting combined with nerve growth factor (NGF) administration at the site of cell transplantation. The results showed that NGF administration significantly promoted the survival of the grafted cells in the host brain and enhanced the content of dopaminergic in the local brain tissue. Behavioral test demonstrated a significant improvement of the motor function of the PD rats after dopaminergic-like cell grafting with NGF administration as compared with that of rats receiving the cell grafting only. These results suggest that transplantation of the dopaminergic- like cells combined with NGF administration may represent a new strategy of stem cell therapy for PD.