Oxidative Stress-Tolerant Stem Cells from Human Exfoliated Deciduous Teeth Decrease Hydrogen Peroxide-Induced Damage in Organotypic Brain Slice Cultures from Adult Mice
Oxidative Stress-Tolerant Stem Cells from Human Exfoliated Deciduous Teeth Decrease Hydrogen Peroxide-Induced Damage in Organotypic Brain Slice Cultures from Adult Mice
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DOI：
10.3390/ijms20081858
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发表时间：
2019-04
影响因子：
5.6
通讯作者：
Li Xiao;C. Saiki;H. Okamura
中科院分区：
文献类型：
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作者：
Li Xiao;C. Saiki;H. Okamura
在缺血性脑损伤（IBD）、创伤性脑损伤（TBI）和神经退行性疾病中，氧化应激引起中枢神经系统的严重组织损伤。在这项研究中，我们使用过氧化氢（H2 O2）诱导的器官型脑片培养（OBSCs）的氧化应激，并探讨氧化应激耐受（OST）干细胞收获的人脱落乳牙（SHED），这是与OBSCs共培养的保护作用。通过荧光染色和免疫组化检测，我们证实了正常SHED和OST-SHED都能阻止H2 O2诱导的细胞死亡，并增加海马中成熟神经元和神经元祖细胞的数量。在共培养过程中，OST-SHED，而不是正常的SHED，表现出神经元细胞形态和表达神经元标记物。ELISA结果显示，正常SHED和OST-SHED均能显著降低H2 O2处理的OBSCs的DNA氧化损伤。SHED还能促进OBSCs产生神经营养因子BDNF（brain derived neurotrophic factor）和IL-6。尽管OST-SHED具有较低的细胞活力，但OST-SHED的神经元保护明显优于正常SHED的神经元保护上级。我们的研究结果表明，SHED，特别是OST-SHED，可以防止氧化应激引起的脑损伤。OST-SHED可作为IBD、TBI和神经退行性疾病的新治疗工具。
Oxidative stress causes severe tissue injury of the central nervous system in ischemic brain damage (IBD), traumatic brain injury (TBI) and neurodegenerative disorders. In this study, we used hydrogen peroxide (H2O2) to induce oxidative stress in organotypic brain slice cultures (OBSCs), and investigated the protective effects of oxidative stress-tolerant (OST) stem cells harvested from human exfoliated deciduous teeth (SHED) which were co-cultivated with OBSCs. Using presto blue assay and immunostaining, we demonstrated that both normal SHED and OST-SHED could prevent H2O2-induced cell death, and increase the numbers of mature neuron and neuronal progenitors in the hippocampus of OBSCs. During co-cultivation, OST-SHED, but not normal SHED, exhibited neuronal cell morphology and expressed neuronal markers. Results from ELISA showed that both normal SHED and OST-SHED significantly decreased oxidative DNA damage in H2O2-treated OBSCs. SHED could also produce neurotrophic factor BDNF (brain derived neurotrophic factor) and promoted the production of IL-6 in OBSCs. Although OST-SHED had lower cell viability, the neuronal protection of OST-SHED was significantly superior to that of normal SHED. Our findings suggest that SHED, especially OST-SHED, could prevent oxidative stress induced brain damage. OST-SHED can be explored as a new therapeutic tool for IBD, TBI and neurodegenerative disorders.