Astrocyte-Like Cells Derived From Human Oral Mucosa Stem Cells Provide Neuroprotection In Vitro and In Vivo
Astrocyte-Like Cells Derived From Human Oral Mucosa Stem Cells Provide Neuroprotection In Vitro and In Vivo
复制标题
DOI：
10.5966/sctm.2013-0074
复制
发表时间：
2014-03-01
影响因子：
6
通讯作者：
Offen, Daniel
中科院分区：
文献类型：
--
作者：
Ganz, Javier;Arie, Ina;Offen, Daniel
人口腔黏膜干细胞（hOMSC）是最近发现的一种神经嵴来源的干细胞群。通过微创手术获得的小活检可产生治疗量的强效hOMSC。我们的目的是评估hOMSC分化为星形细胞样细胞并提供周围神经保护的潜力。我们诱导hOMSC分化为具有星形细胞样形态的细胞，表达星形细胞特征标记物，如胶质纤维酸性蛋白、S100 β和兴奋性氨基酸转运蛋白1，并分泌神经营养因子（NTF），如脑源性神经营养因子、血管内皮生长因子、胶质细胞系源性神经营养因子和胰岛素样生长因子1。条件培养基诱导的细胞可使运动神经元从缺氧或氧化应激中恢复，提示可溶性因子介导的神经保护作用。考虑到细胞的神经元支持能力，将分化后的细胞命名为hOMSC-NS。移植hOMSC-NS后，坐骨神经损伤大鼠运动功能得到改善。在移植物部位，我们发现移植的细胞，NTF水平增加，并且功能神经肌肉连接的显著保存，这是由α -班加罗毒素和突触素共定位证明的。我们的研究结果首次表明，口腔黏膜生成的hOMSC-NS在体外和体内均具有神经保护作用，并指出其未来在神经疾病治疗中的应用。
Human oral mucosa stem cells (hOMSC) are a recently described neural crest-derived stem cell population. Therapeutic quantities of potent hOMSC can be generated from small biopsies obtained by minimally invasive procedures. Our objective was to evaluate the potential of hOMSC to differentiate into astrocyte-like cells and provide peripheral neuroprotection. We induced hOMSC differentiation into cells showing an astrocyte-like morphology that expressed characteristic astrocyte markers as glial fibrillary acidic protein, S100 beta, and the excitatory amino acid transporter 1 and secreted neurotrophic factors (NTF) such as brain-derived neurotrophic factor, vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor 1. Conditioned medium of the induced cells rescued motor neurons from hypoxia or oxidative stress in vitro, suggesting a neuroprotective effect mediated by soluble factors. Given the neuronal support (NS) ability of the cells, the differentiated cells were termed hOMSC-NS. Rats subjected to sciatic nerve injury and transplanted with hOMSC-NS showed improved motor function after transplantation. At the graft site we found the transplanted cells, increased levels of NTF, and a significant preservation of functional neuromuscular junctions, as evidenced by colocalization of alpha-bungarotoxin and synaptophysin. Our findings show for the first time that hOMSC-NS generated from oral mucosa exhibit neuroprotective effects in vitro and in vivo and point to their future therapeutic use in neural disorders.