論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| 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) |