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Tissue-Specific Stem Cells
Version of Record online: 10 DEC 2009
Copyright © 2010 AlphaMed Press
Volume 28, Issue 2, pages 329–343, February 2010
How to Cite
Lee, J. K., Jin, H. K., Endo, S., Schuchman, E. H., Carter, J. E. and Bae, J.-s. (2010), Intracerebral Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells Reduces Amyloid-Beta Deposition and Rescues Memory Deficits in Alzheimer's Disease Mice by Modulation of Immune Responses. STEM CELLS, 28: 329–343. doi: 10.1002/stem.277
Author contributions: H.K.J., J.S.B.: conception and design; H.K.J., J.K.L.: provision of study material and collection of data; H.K.J., J.K.L., S.E., J.S.B.: data analysis and interpretation; H.K.J., J.S.B.: financial support; J.K.L., E.H.S., J.E.C., J.S.B. manuscript writing; H.K.J., E.H.S and J.S.B.: final approval.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS January 28, 2010.
- Issue online: 16 FEB 2010
- Version of Record online: 10 DEC 2009
- Accepted manuscript online: 10 DEC 2009 12:00AM EST
- Manuscript Accepted: 30 NOV 2009
- Manuscript Received: 17 JUL 2009
- Alzheimer's disease model;
- Bone marrow-derived mesenchymal stem cell;
- Amyloid-β; Transplantation;
- Alternatively activated microglia
Alzheimer's disease (AD) is characterized by the deposition of amyloid-β peptide (Aβ) and the formation of neurofibrillary tangles. Transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) has been suggested as a potential therapeutic approach to prevent various neurodegenerative disorders, including AD. However, the actual therapeutic impact of BM-MSCs and their mechanism of action in AD have not yet been ascertained. The aim of this study was therefore to evaluate the therapeutic effect of BM-MSC transplantation on the neuropathology and memory deficits in amyloid precursor protein (APP) and presenilin one (PS1) double-transgenic mice. Here we show that intracerebral transplantation of BM-MSCs into APP/PS1 mice significantly reduced amyloid β-peptide (Aβ) deposition. Interestingly, these effects were associated with restoration of defective microglial function, as evidenced by increased Aβ-degrading factors, decreased inflammatory responses, and elevation of alternatively activated microglial markers. Furthermore, APP/PS1 mice treated with BM-MSCs had decreased tau hyperphosphorylation and improved cognitive function. In conclusion, BM-MSCs can modulate immune/inflammatory responses in AD mice, ameliorate their pathophysiology, and improve the cognitive decline associated with Aβ deposits. These results demonstrate that BM-MSCs are a potential new therapeutic agent for AD. STEM CELLS 2010;28:329–343