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Evaluation of APP695 Transgenic Mice Bone Marrow Mesenchymal Stem Cells Neural Differentiation for Transplantation

机译:APP695转基因小鼠骨髓间充质干细胞的评价术治疗移植术

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摘要

Objective. Even though there is a therapeutic potential to treat Alzheimer’s disease (AD) with neural cell replenishment and replacement, immunological rejections of stem cell transplantation remain a challenging risk. Autologous stem cells from AD patients however may prove to be a promising candidate. Therefore, we studied the neuronal differentiation efficiency of bone marrow mesenchymal stem cells (MSCs) from APP695 transgenic mice, which share features of human AD. Method. Cultured MSCs from APP695 transgenic mice are used; neuronal differentiation was assessed by immunocytochemistry and Western blot. Correlation with Notch signaling was examined. Autophage flux was assessed by western blot analysis. Results. MSCs from APP695 mice have higher neuronal differentiation efficiency than MSCs from wild type mice (WT MSCs). The expression of Notch-1 signaling decreased during the differentiation process. However, autophagy flux, which is essential for neuronal cell survival and neuronal function, was impaired in the neuronally differentiated counterparts of APP695 MSCs (APP695 MSCs–n). Conclusion. These results suggested autologous MSCs of APP690 mice may not be a good candidate for cell transplantation.
机译:客观的。尽管存在治疗阿尔茨海默病(AD)具有神经细胞补充和更换的治疗潜力,但干细胞移植的免疫抑制仍然是一个具有挑战性的风险。然而,来自AD患者的自体干细胞可能被证明是一个有前途的候选人。因此,我们研究了来自APP695转基因小鼠的骨髓间充质干细胞(MSCs)的神经元分化效率,该小鼠占据人广告的特征。方法。使用APP695转基因小鼠的培养MSC;通过免疫细胞化学和Western印迹评估神经元分化。检查与缺口信令的相关性。通过Western印迹分析评估了自胸助焊剂。结果。来自APP695小鼠的MSCs具有比来自野生型小鼠(WT MSC)的MSC的神经元分化效率更高。在分化过程期间,Notch-1信号传导的表达降低。然而,在APP695 MSCs的神经分化的对应物中,对神经元细胞存活和神经元功能至关重要的自噬助焊剂(APP695 MSCS-N)。结论。这些结果表明APP690小鼠的自体MSC可能不是细胞移植的良好候选者。

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