期刊
BEHAVIOURAL BRAIN RESEARCH
卷 293, 期 -, 页码 189-197出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2015.07.043
关键词
Alzheimer's disease; Dental pulp stem cells; Stem cell-conditioned medium; Microglia; Intranasal administration
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Ministry of Health, Labour, and Welfare of Japan
- Grants-in-Aid for Scientific Research [26670863, 25293408] Funding Source: KAKEN
Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by a decline in cognitive abilities and the appearance of beta-amyloid plagues in the brain. Although the pathogenic mechanisms associated with AD are not fully understood, activated microglia releasing various neurotoxic factors, including pro-inflammatory cytokines and oxidative stress mediators, appear to play major roles. Here, we investigated the therapeutic benefits of a serum-free conditioned medium (CM) derived from the stem cells of human exfoliated deciduous teeth (SHEDs) in a mouse model of AD. The intranasal administration of SHEDs in these mice resulted in substantially improved cognitive function. SHED-CM contained factors involved in multiple neuroregenerative mechanisms, such as neuroprotection, axonal elongation, neurotransmission, the suppression of inflammation, and microglial regulation. Notably, SHED-CM attenuated the pro-inflammatory responses induced by beta-amyloid plagues, and generated an anti-inflammatory/tissue-regenerating environment, which was accompanied by the induction of anti-inflammatory M2-like microglia. Our data suggest that SHED-CM may provide significant therapeutic benefits for AD. (C) 2015 Elsevier B.V. All rights reserved.
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