title: Human umbilical cord mesenchymal stem cell-derived neuron-like cells rescue memory deficits and reduce amyloid-beta deposition in an AβPP/PS1 transgenic mouse model.
abstract: BACKGROUND
  Cell therapy is a potential therapeutic approach for neurodegenerative disorders, such as Alzheimer disease (AD). Neuronal differentiation of stem cells before transplantation is a promising procedure for cell therapy. However, the therapeutic impact and mechanisms of action of neuron-like cells differentiated from human umbilical cord mesenchymal stem cells in AD have not been determined.
  
  
  METHODS
  In this study, we used tricyclodecan-9-yl-xanthogenate (D609) to induce human mesenchymal stem cells isolated from Wharton jelly of the umbilical cord (HUMSCs) to differentiate into neuron-like cells (HUMSC-NCs), and transplanted the HUMSC-NCs into an AβPP/PS1 transgenic AD mouse model. The effects of HUMSC-NC transplantation on the cognitive function, synapsin I level, amyloid β-peptides (Aβ) deposition, and microglial function of the mice were investigated.
  
  
  RESULTS
  We found that transplantation of HUMSC-NCs into AβPP/PS1 mice improved the cognitive function, increased synapsin I level, and significantly reduced Aβ deposition in the mice. The beneficial effects were associated with "alternatively activated" microglia (M2-like microglia). In the mice transplanted with HUMSC-NCs, M2-like microglial activation was significantly increased, and the expression of antiinflammatory cytokine associated with M2-like microglia, interleukin-4 (IL-4), was also increased, whereas the expression of proinflammatory cytokines associated with classic microglia (M1-like microglia), including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), was significantly reduced. Moreover, the expression of Aβ-degrading factors, insulin-degrading enzyme (IDE) and neprilysin (NEP), was increased substantially in the mice treated with HUMSC-NCs.
  
  
  CONCLUSIONS
  HUMSC-NC transplantation decreased Aβ deposition and improved memory in AβPP/PS1 mice by a mechanism associated with activating M2-like microglia and modulating neuroinflammation. Transplantation of neuron-like cells differentiated from mesenchymal stem cells might be a promising cell therapy for Alzheimer disease.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: ZhaoHong
authors.initials: Z
authors.lastname: Xie
authors.forename: LiFei
authors.initials: L
authors.lastname: Wei
authors.forename: HongNa
authors.initials: H
authors.lastname: Yang
authors.forename: ShaoNan
authors.initials: S
authors.lastname: Yang
authors.forename: ZhengYu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: CuiPing
authors.initials: C
authors.lastname: Zhao
authors.forename: JianZhong
authors.initials: J
authors.lastname: Bi
mesh_terms: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; C580804:presenilin 1, mouse