| RRC ID |
31847
|
| 著者 |
Takamatsu K, Ikeda T, Haruta M, Matsumura K, Ogi Y, Nakagata N, Uchino M, Ando Y, Nishimura Y, Senju S.
|
| タイトル |
Degradation of amyloid beta by human induced pluripotent stem cell-derived macrophages expressing Neprilysin-2.
|
| ジャーナル |
Stem Cell Res
|
| Abstract |
The purpose of this study was to evaluate the therapeutic potential of human induced pluripotent stem (iPS) cell-derived macrophage-like cells for Alzheimer's disease (AD). In previous studies, we established the technology to generate macrophage-like myeloid lineage cells with proliferating capacity from human iPS cells, and we designated the cells iPS-ML. iPS-ML reduced the level of Aβ added into the culture medium, and the culture supernatant of iPS-ML alleviated the neurotoxicity of Aβ. We generated iPS-ML expressing the Fc-receptor-fused form of a single chain antibody specific to Aβ. In addition, we made iPS-ML expressing Neprilysin-2 (NEP2), which is a protease with Aβ-degrading activity. In vitro, expression of NEP2 but not anti-Aβ scFv enhanced the effect to reduce the level of soluble Aβ oligomer in the culture medium and to alleviate the neurotoxicity of Aβ. To analyze the effect of iPS-ML expressing NEP2 (iPS-ML/NEP2) in vivo, we intracerebrally administered the iPS-ML/NEP2 to 5XFAD mice, which is a mouse model of AD. We observed significant reduction in the level of Aβ in the brain interstitial fluid following administration of iPS-ML/NEP2. These results suggested that iPS-ML/NEP2 may be a potential therapeutic agent in the treatment of AD.
|
| 巻・号 |
13(3 Pt A)
|
| ページ |
442-53
|
| 公開日 |
2014-11-1
|
| DOI |
10.1016/j.scr.2014.10.001
|
| PII |
S1873-5061(14)00111-1
|
| PMID |
25460605
|
| MeSH |
Alzheimer Disease / metabolism
Alzheimer Disease / pathology
Amyloid beta-Peptides / metabolism*
Animals
Antigens, CD / metabolism
Cell Differentiation
Cells, Cultured
Disease Models, Animal
Flow Cytometry
Hippocampus / metabolism
Hippocampus / pathology
Humans
Induced Pluripotent Stem Cells / cytology*
Induced Pluripotent Stem Cells / transplantation
Macrophages / cytology
Macrophages / immunology
Macrophages / metabolism*
Mice
Microscopy, Fluorescence
Neprilysin / genetics
Neprilysin / metabolism*
Transplantation, Heterologous
|
| IF |
4.495
|
| 引用数 |
22
|
|
WOS 分野
|
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
CELL & TISSUE ENGINEERING
CELL BIOLOGY
|
| リソース情報 |
| 遺伝子材料 |
W01A023B19 (HGE009243)
CSII-EF-RfA (RDB04387)
pCAG-HIVgp (RDB04394)
pCMV-VSV-G-RSV-Rev (RDB04393) |
