Degradation of amyloid beta by human induced pluripotent stem cell-derived macrophages expressing Neprilysin-2

作者：Takamatsu Koutaro^*; Ikeda Tokunori; Haruta Miwa; Matsumura Keiko; Ogi Yasuhiro; Nakagata Naomi; Uchino Makoto; Ando Yukio; Nishimura Yasuharu; Senju Satoru

来源：Stem Cell Research, 2014, 13(3): 442-453.

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%26apos;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 A beta added into the culture medium, and the culture supernatant of iPS-ML alleviated the neurotoxicity of A beta. We generated iPS-ML expressing the Fc-receptor-fused form of a single chain antibody specific to A beta. In addition, we made iPS-ML expressing Neprilysin-2 (NEP2), which is a protease with A beta-degrading activity. In vitro, expression of NEP2 but not anti-A beta scFv enhanced the effect to reduce the level of soluble A beta oligomer in the culture medium and to alleviate the neurotoxicity of A beta. 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 A beta 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.

• 出版日期2014-11