Midbrain Neural Stem Cells Show Unique Cell Survival, Neuronal Commitment and Neurotrophic Properties with Therapeutic Potential forParkinson' s Disease
Midbrain Neural Stem Cells Show Unique Cell Survival, Neuronal Commitment and Neurotrophic Properties with Therapeutic Potential forParkinson' s Disease
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DOI：
10.4172/2161-0460.s10-001
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发表时间：
2012-02
期刊：
影响因子：
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通讯作者：
Yinxiu Ding;Li-Chun Wei;Yong-Hong Liu;L. Duan;X. Jiao;Yi Xia;Liang-Wei Chen
中科院分区：
文献类型：
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作者：
Yinxiu Ding;Li-Chun Wei;Yong-Hong Liu;L. Duan;X. Jiao;Yi Xia;Liang-Wei Chen
帕金森病（Parkinson's disease，PD）是一种严重的神经衰弱性疾病，其主要原因是黑质多巴胺能神经元大量进行性变性丢失，新的细胞疗法有望恢复受损的多巴胺能神经元系统的功能，治愈PD。为了研究神经干细胞在帕金森病移植治疗中的应用潜力，本研究采用体外培养的方法，对中脑源性神经干细胞（midbrain-derived neural stem cells，mNSCs）的增殖、分化和神经营养特性进行了研究，并与海马源性神经干细胞（hNSCs）进行了比较。结果显示：（1）mNSCs在无血清培养条件下，BrdU掺入率和增殖率均低于hNSCs，但细胞存活率高于hNSCs：（2）mNSCs在分化d1-d 7时，Tuj-1+未成熟神经元分化率与hNSCs相似，但Nurr 1+和TH+细胞命运定型率高于hNSCs; 3）mNSCs表达脑源性神经营养因子（brainderived neurotrophic factor，BDNF）、胶质源性神经营养因子（glial-derived neurotrophic factor，GDNF）、脑多巴胺神经营养因子（cerebral dopamine neurotrophic factor，CDNF）和DJ-1等多种神经营养因子，这些因子在多巴胺能神经元的维持或神经保护中发挥积极作用，其表达水平与hNSCs略有不同或相似。总之，本研究为mNSCs具有独特的细胞增殖、细胞存活、多巴胺能神经元分化和神经营养特性提供了新的证据，提示中脑源性NSCs可能为人类PD的治疗性细胞移植或神经保护治疗提供理想的细胞来源或可靠的组织候选。
Parkinson’s disease (PD) is one severe debilitating neurological disease that results from massive and progressive degenerative loss of dopaminergic neurons in the substantial nigra, and new cell therapy appeal hopeful functional recovery of injured dopaminergic neuronal system and cure of PD. We are interested in therapeutic potential of neural stem cell in transplantation treatment against PD, the midbrain-derived neural stem cells (mNSCs) were studied by in vitro culture in focusing on their proliferative, differentiation and neurotrophic properties and in comparing with hippocampus-derived NSCs (hNSCs). The results revealed that: 1) The mNSCs showed lower BrdU incorporation ratio or lower proliferative rate than that of hippocampus-derived ones but had higher cell survival capacity in serum-free culture; 2) The mNSCs exhibited similar Tuj-1+ immature neuronal differentiation, but higher Nurr1+ and tyrosine hydroxylase (TH)+ cell fate commitment in comparison with that of hNSCs in at d1-d7 differentiation culture; 3) The mNSCs expressed several neurotrophic factors, i.e. brainderived neurotrophic factor(BDNF), glial-derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF) and DJ-1, that actively function in dopaminergic neuronal maintenance or neuroprotection, with their slightly different or similar levels in comparison to that of hNSCs. Taken together, this study has provided new evidence that mNSCs show the unique cell proliferation, cell survival, dopaminergic neuronal differentiation and neurotrophic properties, suggesting that midbrain-derived NSCs may present an ideal cell source or reliable tissue candidate for therapeutic cell transplantation or neuroprotective treatment of PD in human beings.