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Publication : Long-term immunomodulatory effect of amniotic stem cells in an Alzheimer's disease model.

First Author  Kim KS Year  2013
Journal  Neurobiol Aging Volume  34
Issue  10 Pages  2408-20
PubMed ID  23623603 Mgi Jnum  J:211731
Mgi Id  MGI:5576097 Doi  10.1016/j.neurobiolaging.2013.03.029
Citation  Kim KS, et al. (2013) Long-term immunomodulatory effect of amniotic stem cells in an Alzheimer's disease model. Neurobiol Aging 34(10):2408-20
abstractText  Amyloid beta (Abeta) plays a major role in Alzheimer's disease (AD), and neuroinflammatory processes mediated by Abeta 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-beta 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 Abeta plaques in brain. The number of ED1-positive phagocytic microglial cells associated with Abeta plaques was higher in AMSC-injected mice than in phosphate-buffered saline-injected mice, and the level of Abeta-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-alpha, was lower and that of anti-inflammatory cytokines, interleukin-10 and transforming growth factor-beta, 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.
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