title: Long-term immunomodulatory effect of amniotic stem cells in an Alzheimer's disease model.
abstract: Amyloid beta (Aβ) plays a major role in Alzheimer's disease (AD), and neuroinflammatory processes mediated by Aβ plaque-induced microglial cells and astrocytes contribute to AD pathogenesis. The present study examined human placenta amniotic membrane-derived mesenchymal stem cells (AMSCs), which have potent immunomodulatory and paracrine effects in a Tg2576 (APPswe) transgenic mouse model of AD. AMSCs secreted high levels of transforming growth factor-β under in vitro inflammatory environment conditions. Six weeks after the intravenous injection of AMSCs, APPswe mice showed evidence of improved spatial learning, which significantly correlated with the observation of fewer Aβ plaques in brain. The number of ED1-positive phagocytic microglial cells associated with Aβ plaques was higher in AMSC-injected mice than in phosphate-buffered saline-injected mice, and the level of Aβ-degrading enzymes (matrix metallopeptidase-9 and insulin-degrading enzyme) was also significantly higher. Furthermore, the level of proinflammatory cytokines, interleukin-1 and tumor necrosis factor-α, was lower and that of anti-inflammatory cytokines, interleukin-10 and transforming growth factor-β, was higher in AMSC-injected mice than phosphate-buffered saline-injected mice. These effects lasted until 12 weeks after AMSC injection. Taken together, these results collectively suggest that injection of AMSCs might show significant long-lasting improvement in AD pathology and memory function via immunomodulatory and paracrine mechanisms.
authors.affiliation: Department of Bioengineering, College of Life Science, CHA University, Seoul, Korea.
authors.forename: Kyung-Sul
authors.initials: KS
authors.lastname: Kim
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Park
authors.forename: Han Wool
authors.initials: HW
authors.lastname: Kim
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Park
authors.forename: Hyun-Seob
authors.initials: HS
authors.lastname: Lee
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Lim
authors.forename: Tae Hee
authors.initials: TH
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
authors.forename: Jisook
authors.initials: J
authors.lastname: Moon
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000523:psychology / Q000628:therapy*; D000650:Amnion / Q000166:cytology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D056747:Immunomodulation; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008568:Memory; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D019899:Paracrine Communication; D058225:Plaque, Amyloid / Q000378:metabolism; D011247:Pregnancy; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018836:Inflammation Mediators; D016212:Transforming Growth Factor beta
keywords: Alzheimer's disease; Amyloid beta; Human placenta amniotic membrane-derived mesenchymal stem cells; Immunomodulation; Paracrine effect