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Stem Cells Transl Med. 2017 Jan;6(1):293-305. doi: 10.5966/sctm.2016-0081. Epub 2016 Aug 15.

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

Author information

1
Department of Biochemistry and Biomedical Sciences, Seoul National University, Seoul, Republic of Korea.
2
Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Republic of Korea.
3
National Research Laboratory for Stem Cell Niche, Seoul National University, Seoul, Republic of Korea.
4
Department of New Biology and Center for Plant and Aging Research, Institute for Basic Science, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea.
5
The Korean Ginseng Research Institute, Daejeon, Republic of Korea.
6
Department of Biochemistry, College of Medicine, Konyang University, Daejeon, Republic of Korea.
7
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, School of Medicine and School of Pharmacy, Seoul National University, Seoul, Republic of Korea.

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.

KEYWORDS:

5XFAD mice; Alzheimer's disease; Oligodendrocyte; Protein-iPSC; Proteomic analysis

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