Protein-Induced Pluripotent Stem Cells Ameliorate and Reduce Aβ Deposition of Alzheimer's Disease

被引:63
作者
Cha, Moon-Yong [1 ]
Kwon, Yoo-Wook [5 ]
Ahn, Hyo-Suk [2 ]
Jeong, Hyobin [6 ,7 ]
Lee, Yong Yook [8 ]
Moon, Minho [9 ]
Baik, Sung Hoon [1 ]
Kim, Dong Kyu [1 ]
Song, Hyundong [1 ]
Yi, Eugene C. [3 ,4 ]
Hwang, Daehee [6 ,7 ]
Kim, Hyo-Soo [2 ,3 ,4 ,5 ]
Mook-Jung, Inhee [1 ]
机构
[1] Seoul Natl Univ, Sch Med, Grad Sch Convergence Sci & Technol, Dept Biochem & Biomed Sci, Seoul, South Korea
[2] Seoul Natl Univ, Sch Med, Grad Sch Convergence Sci & Technol, Natl Lab Stem Cell Niche, Seoul, South Korea
[3] Seoul Natl Univ, Sch Med, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, Seoul, South Korea
[4] Seoul Natl Univ, Sch Med, Seoul, South Korea
[5] Seoul Natl Univ Hosp, Innovat Res Inst Cell Therapy, Seoul, South Korea
[6] Daegu Gyeongbuk Inst Sci & Technol, Inst Basic Sci Daegu, Dept New Biol, Daegu, South Korea
[7] Daegu Gyeongbuk Inst Sci & Technol, Inst Basic Sci Daegu, Ctr Plant & Aging Res, Daegu, South Korea
[8] Korean Ginseng Res Inst, Daejeon, South Korea
[9] Konyang Univ, Coll Med, Dept Biochem, Daejeon, South Korea
关键词
Alzheimer's disease; Protein-iPSC; 5XFAD mice; Proteomic analysis; Oligodendrocyte; CENTRAL-NERVOUS-SYSTEM; AMYLOID-BETA; PROGENITOR CELLS; OLIGODENDROCYTE; ACTIVATION; MOUSE; MICE; IDENTIFICATION; MECHANISMS; GENERATION;
D O I
10.5966/sctm.2016-0081
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:293 / 305
页数:13
相关论文
共 59 条
[1]   Gene Ontology: tool for the unification of biology [J].
Ashburner, M ;
Ball, CA ;
Blake, JA ;
Botstein, D ;
Butler, H ;
Cherry, JM ;
Davis, AP ;
Dolinski, K ;
Dwight, SS ;
Eppig, JT ;
Harris, MA ;
Hill, DP ;
Issel-Tarver, L ;
Kasarskis, A ;
Lewis, S ;
Matese, JC ;
Richardson, JE ;
Ringwald, M ;
Rubin, GM ;
Sherlock, G .
NATURE GENETICS, 2000, 25 (01) :25-29
[2]   Biology of oligodendrocyte and myelin in the mammalian central nervous system [J].
Baumann, N ;
Pham-Dinh, D .
PHYSIOLOGICAL REVIEWS, 2001, 81 (02) :871-927
[3]   Dynamic changes in myelin aberrations and oligodendrocyte generation in chronic amyloidosis in mice and men [J].
Behrendt, Gwendolyn ;
Baer, Kristin ;
Buffo, Annalisa ;
Curtis, Maurice A. ;
Faull, Richard L. ;
Rees, Mark I. ;
Goetz, Magdalena ;
Dimou, Leda .
GLIA, 2013, 61 (02) :273-286
[4]   Neuronal development is promoted by weakened intrinsic antioxidant defences due to epigenetic repression of Nrf2 [J].
Bell, Karen F. S. ;
Al-Mubarak, Bashayer ;
Martel, Marc-Andre ;
McKay, Sean ;
Wheelan, Nicola ;
Hasel, Philip ;
Markus, Nora M. ;
Baxter, Paul ;
Deighton, Ruth F. ;
Serio, Andrea ;
Bilican, Bilada ;
Chowdhry, Sudhir ;
Meakin, Paul J. ;
Ashford, Michael L. J. ;
Wyllie, David J. A. ;
Scannevin, Robert H. ;
Chandran, Siddharthan ;
Hayes, John D. ;
Hardingham, Giles E. .
NATURE COMMUNICATIONS, 2015, 6
[5]   The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes [J].
Benilova, Iryna ;
Karran, Eric ;
De Strooper, Bart .
NATURE NEUROSCIENCE, 2012, 15 (03) :349-357
[6]   A comparison of normalization methods for high density oligonucleotide array data based on variance and bias [J].
Bolstad, BM ;
Irizarry, RA ;
Åstrand, M ;
Speed, TP .
BIOINFORMATICS, 2003, 19 (02) :185-193
[7]   Neural Stem Cells: Historical Perspective and Future Prospects [J].
Breunig, Joshua J. ;
Haydar, Tank F. ;
Rakic, Pasko .
NEURON, 2011, 70 (04) :614-625
[8]   A transcriptome database for astrocytes, neurons, and oligodendrocytes: A new resource for understanding brain development and function [J].
Cahoy, John D. ;
Emery, Ben ;
Kaushal, Amit ;
Foo, Lynette C. ;
Zamanian, Jennifer L. ;
Christopherson, Karen S. ;
Xing, Yi ;
Lubischer, Jane L. ;
Krieg, Paul A. ;
Krupenko, Sergey A. ;
Thompson, Wesley J. ;
Barres, Ben A. .
JOURNAL OF NEUROSCIENCE, 2008, 28 (01) :264-278
[9]   Down-Regulation of Amyloid-β Through AMPK Activation by Inhibitors of GSK-3β in SH-SY5Y and SH-SY5Y-AβPP695 Cells [J].
Cai, Zhiyou ;
Li, Benyi ;
Li, Keshen ;
Zhao, Bin .
JOURNAL OF ALZHEIMERS DISEASE, 2012, 29 (01) :89-98
[10]   Induction of pluripotent stem cells from adult somatic cells by protein-based reprogramming without genetic manipulation [J].
Cho, Hyun-Jai ;
Lee, Choon-Soo ;
Kwon, Yoo-Wook ;
Paek, Jae Seung ;
Lee, Sun-Hee ;
Hur, Jin ;
Lee, Eun Ju ;
Roh, Tae-Young ;
Chu, In-Sun ;
Leem, Sun-Hee ;
Kim, Youngsoo ;
Kang, Hyun-Jae ;
Park, Young-Bae ;
Kim, Hyo-Soo .
BLOOD, 2010, 116 (03) :386-395