Degradation of amyloid beta by human induced pluripotent stem cell-derived macrophages expressing Neprilysin-2.
- Authors
- Takamatsu, Koutaro; Ikeda, Tokunori; Haruta, Miwa; Matsumura, Keiko; Ogi, Yasuhiro; Nakagata, Naomi; Uchino, Makoto; Ando, Yukio; Nishimura, Yasuharu; Senju, Satoru
- Year
- 2014
- Journal
- Stem cell research
- PMID
- 25460605
- DOI
- 10.1016/j.scr.2014.10.001
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 AΞ² added into the culture medium, and the culture supernatant of iPS-ML alleviated the neurotoxicity of AΞ². We generated iPS-ML expressing the Fc-receptor-fused form of a single chain antibody specific to AΞ². In addition, we made iPS-ML expressing Neprilysin-2 (NEP2), which is a protease with AΞ²-degrading activity. In vitro, expression of NEP2 but not anti-AΞ² scFv enhanced the effect to reduce the level of soluble AΞ² oligomer in the culture medium and to alleviate the neurotoxicity of AΞ². 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 AΞ² 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.
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