Protein-Induced Pluripotent Stem Cells Ameliorate Cognitive Dysfunction and Reduce Aβ Deposition in a Mouse Model of Alzheimer's Disease

蛋白质诱导的多能干细胞改善阿尔茨海默病小鼠模型的认知功能障碍并减少 Aβ 沉积

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作者:Moon-Yong Cha, Yoo-Wook Kwon, Hyo-Suk Ahn, Hyobin Jeong, Yong Yook Lee, Minho Moon, Sung Hoon Baik, Dong Kyu Kim, Hyundong Song, Eugene C Yi, Daehee Hwang, Hyo-Soo Kim, Inhee Mook-Jung

Abstract

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.

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