title: Wharton's Jelly-derived mesenchymal stem cells alleviate memory deficits and reduce amyloid-β deposition in an APP/PS1 transgenic mouse model.
abstract: Alzheimer's disease (AD) is the leading cause of dementia in the elderly and is characterized by amyloid plaques, neurofibrillary tangles, and neuronal loss. Cumulative evidence supports that neuroinflammation is an important factor for the pathogenesis of AD and contributes to amyloid beta (Aβ) generation. However, there has been no effective treatment for AD. Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) have a potential therapeutic effect in the treatment for neurological diseases. In the present study, we evaluated the therapeutic effect of WJ-MSC transplantation on the neuropathology and memory deficits in amyloid precursor protein (APP) and presenilin-1 (PS1) double-transgenic mice and discussed the mechanism. WJ-MSCs were intravenously transplanted into the APP/PS1 mice. Four weeks after treatment, WJ-MSCs significantly improved the spatial learning and alleviated the memory decline in the APP/PS1 mice. Aβ deposition and soluble Aβ levels were significantly reduced after WJ-MSC treatment. Furthermore, WJ-MSCs significantly increased the expression of the anti-inflammatory cytokine, IL-10. Meanwhile, pro-inflammatory microglial activation and the expressions of pro-inflammatory cytokines, IL-1β and TNFα, were significantly down-regulated by WJ-MSC treatment. Thus, our findings suggest that WJ-MSCs might produce beneficial effects on the prevention and treatment for AD through modulation of neuroinflammation.
authors.affiliation: Department of Neurology, The Second Hospital of Shandong University, 247#, Beiyuan Dajie, Jinan, 250033, China.
authors.forename: Zhao-Hong
authors.initials: ZH
authors.lastname: Xie
authors.affiliation: Department of Neurology, The Second Hospital of Shandong University, 247#, Beiyuan Dajie, Jinan, 250033, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Jinan Central Hospital, 105#, Jiefang Road, Jinan, 250013, China.
authors.forename: Xiao-Ran
authors.initials: XR
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Second Hospital of Shandong University, 247#, Beiyuan Dajie, Jinan, 250033, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Neurology, The Second Hospital of Shandong University, 247#, Beiyuan Dajie, Jinan, 250033, China.
authors.forename: Li-Fei
authors.initials: LF
authors.lastname: Wei
authors.affiliation: Department of Neurology, The Second Hospital of Shandong University, 247#, Beiyuan Dajie, Jinan, 250033, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Second Hospital of Shandong University, 247#, Beiyuan Dajie, Jinan, 250033, China.
authors.forename: Shun-Liang
authors.initials: SL
authors.lastname: Xu
authors.affiliation: Department of Neurology, The Second Hospital of Shandong University, 247#, Beiyuan Dajie, Jinan, 250033, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Neurology, The Second Hospital of Shandong University, 247#, Beiyuan Dajie, Jinan, 250033, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Lai
authors.affiliation: Department of Neurology, The Second Hospital of Shandong University, 247#, Beiyuan Dajie, Jinan, 250033, China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Bi
authors.affiliation: Department of Neurology, The Second Hospital of Shandong University, 247#, Beiyuan Dajie, Jinan, 250033, China. xiaoyunwww@126.com.
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Wang
mesh_terms: D061605:Administration, Intravenous; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D008569:Memory Disorders / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics*; D065853:Spatial Learning / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods*; D059631:Wharton Jelly / Q000166:cytology*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016207:Cytokines; D053764:Presenilin-1
keywords: Alzheimer’s disease; Amyloid beta; Interleukin-10; Microglia; Neuroinflammation; Wharton’s Jelly-derived mesenchymal stem cells