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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
Abstract
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.
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Metadata
- Authors
- Lee, J. K., Jin, H. K., Endo, S., Schuchman, E. H., Carter, J. E., & Bae, J.-S.
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-12-10
- Volume
- 28
- Issue
- 2
- Pages
- 329-343
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W1981195723
- Cited by
- 304
- References
- 25
- FWCI
- 9.25
- Type
- journal article
- Language
- en
- Open access
- closed
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