RRC ID 31847
Author Takamatsu K, Ikeda T, Haruta M, Matsumura K, Ogi Y, Nakagata N, Uchino M, Ando Y, Nishimura Y, Senju S.
Title Degradation of amyloid beta by human induced pluripotent stem cell-derived macrophages expressing Neprilysin-2.
Journal 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.
Volume 13(3 Pt A)
Pages 442-53
Published 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
Times Cited 22
DNA material W01A023B19 (HGE009243) CSII-EF-RfA (RDB04387) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393)