Protein-Induced Pluripotent Stem Cells Ameliorate Cognitive Dysfunction and Reduce Aβ Deposition in a Mouse Model of Alzheimer's Disease.
Protein-Induced Pluripotent Stem Cells Ameliorate Cognitive Dysfunction and Reduce Aβ Deposition in a Mouse Model of Alzheimer's Disease.
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DOI：
10.5966/sctm.2016-0081
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发表时间：
2017-01
影响因子：
6
通讯作者：
Mook-Jung I
中科院分区：
文献类型：
--
作者：
Cha MY;Kwon YW;Ahn HS;Jeong H;Lee YY;Moon M;Baik SH;Kim DK;Song H;Yi EC;Hwang D;Kim HS;Mook-Jung I
干细胞移植入脑通过细胞替代、特定神经递质的释放和神经营养因子的产生来减轻中枢神经系统的功能缺陷。为了确定用于治疗阿尔茨海默病（AD）的患者特异性和安全的干细胞，我们通过处理胚胎干细胞的蛋白质提取物，从小鼠皮肤成纤维细胞中获得了诱导多能干细胞（iPSCs）。这些重编程细胞是多能性的，但非致瘤性的。在这里，我们报道了蛋白- iPSCs在5XFAD转基因AD小鼠模型中分化为胶质细胞并减少斑块沉积。我们还发现，移植的蛋白质- iPSCs减轻了这些小鼠的认知功能障碍。蛋白质组学分析显示，在注射了蛋白质- iPSCs的大脑中，少突胶质细胞相关基因上调，为蛋白质- iPSCs的潜在功能提供了新的见解。综上所述，我们的数据表明，蛋白质- iPSCs可能是一种很有前景的治疗阿尔茨海默病的方法。干细胞转化医学2017；6:293 - 305
Transplantation of stem cells into the brain attenuates functional deficits in the central nervous system via cell replacement, the release of specific neurotransmitters, and the production of neurotrophic factors. To identify patient‐specific and safe stem cells for treating Alzheimer's disease (AD), we generated induced pluripotent stem cells (iPSCs) derived from mouse skin fibroblasts by treating protein extracts of embryonic stem cells. These reprogrammed cells were pluripotent but nontumorigenic. Here, we report that protein‐iPSCs differentiated into glial cells and decreased plaque depositions in the 5XFAD transgenic AD mouse model. We also found that transplanted protein‐iPSCs mitigated the cognitive dysfunction observed in these mice. Proteomic analysis revealed that oligodendrocyte‐related genes were upregulated in brains injected with protein‐iPSCs, providing new insights into the potential function of protein‐iPSCs. Taken together, our data indicate that protein‐iPSCs might be a promising therapeutic approach for AD. Stem Cells Translational Medicine 2017;6:293–305