Multipotentiality, homing properties, and pyramidal neurogenesis of CNS-derived LeX(ssea-1)+/CXCR4+ stem cells

Multipotentiality, homing properties, and pyramidal neurogenesis of CNS-derived LeX(ssea-1)+/CXCR4+ stem cells
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DOI:
10.1096/fj.05-4170fje
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发表时间:
2005-09-01
期刊:
影响因子:
4.8
通讯作者:
Comi, GP
Comi, GP
中科院分区:
生物学2区
文献类型:
--
作者:
Corti, S;Locatelli, F;Comi, GP

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实现神经干细胞在整个中枢神经系统(CNS)的有效分布和特异性神经元的稳健生成是神经退行性疾病细胞介导治疗发展的主要挑战。我们分离了一个原始神经干细胞亚群,LeX(Le)和CXCR4(CX)抗原双阳性,具有中枢神经系统归巢潜力和广泛的神经元再生能力。Le(+)CX(+)细胞是多电位细胞,可以生成神经元以及肌源性细胞和内皮细胞。体内Le(+)CX(+)细胞广泛结合并分化为皮质和海马锥体神经元。由于静脉输送可能是一种侵入性较小的移植途径,我们研究了Le(+)CX(+)细胞是否可以跨内皮单层迁移。脑内共给药SDF使静脉注射的Le(+) CX+细胞迁移到中枢神经系统,少量但显著的供体细胞分化为神经元。特定神经干细胞群的分离可以为神经元替代策略提供主要优势。
Achieving efficient distribution of neural stem cells throughout the central nervous system (CNS) and robust generation of specific neurons is a major challenge for the development of cell-mediated therapy for neurodegenerative diseases. We isolated a primitive neural stem cell subset, double positive for LeX(Le) and CXCR4(CX) antigens that possesses CNS homing potential and extensive neuronal repopulating capacity. Le(+)CX(+) cells are multipotential and can generate neurons as well as myogenic and endothelial cells. In vivo Le(+)CX(+) cells displayed widespread incorporation and differentiated into cortical and hippocampal pyramidal neurons. Since intravenous delivery could be a less invasive route of transplantation, we investigated whether Le(+)CX(+) cells could migrate across endothelial monolayers. Intracerebral coadministration of SDF enabled migration of intravenously injected Le(+) CX+ cells into the CNS and a small, yet significant, number of donor cells differentiated into neurons. The isolation of a specific neural stem cell population could offer major advantages to neuronal replacement strategies.