Protein-Induced Pluripotent Stem Cells Ameliorate Cognitive Dysfunction and Reduce Aβ Deposition in a Mouse Model of Alzheimer's Disease.
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.
Department of Biochemistry and Biomedical Sciences, Seoul National University, Seoul, Republic of Korea.
Moon-Yong
MY
Cha
Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Republic of Korea.
Yoo-Wook
YW
Kwon
National Research Laboratory for Stem Cell Niche, Seoul National University, Seoul, Republic of Korea.
Hyo-Suk
HS
Ahn
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.
Hyobin
H
Jeong
The Korean Ginseng Research Institute, Daejeon, Republic of Korea.
Yong Yook
YY
Lee
Department of Biochemistry, College of Medicine, Konyang University, Daejeon, Republic of Korea.
Minho
M
Moon
Department of Biochemistry and Biomedical Sciences, Seoul National University, Seoul, Republic of Korea.
Sung Hoon
SH
Baik
Department of Biochemistry and Biomedical Sciences, Seoul National University, Seoul, Republic of Korea.
Dong Kyu
DK
Kim
Department of Biochemistry and Biomedical Sciences, Seoul National University, Seoul, Republic of Korea.
Hyundong
H
Song
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.
Eugene C
EC
Yi
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.
Daehee
D
Hwang
Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Republic of Korea.|National Research Laboratory for Stem Cell Niche, Seoul National University, Seoul, Republic of Korea.|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.
Hyo-Soo
HS
Kim
Department of Biochemistry and Biomedical Sciences, Seoul National University, Seoul, Republic of Korea.
Inhee
I
Mook-Jung
D000544:Alzheimer Disease / Q000503:physiopathology* / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D002454:Cell Differentiation; D060825:Cognitive Dysfunction / Q000150:complications / Q000628:therapy*; D004195:Disease Models, Animal; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism; D058225:Plaque, Amyloid / Q000473:pathology; D020543:Proteome / Q000378:metabolism; D033581:Stem Cell Transplantation; D014168:Transferrin / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D016229:Amyloid beta-Peptides; D020543:Proteome; D014168:Transferrin
5XFAD mice; Alzheimer's disease; Oligodendrocyte; Protein-iPSC; Proteomic analysis