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

Jong Kil Lee, Hee Kyung Jin, Shogo Endo, Edward H. Schuchman, Janet E. Carter, Jae Sung Bae

Research output: Contribution to journalArticlepeer-review

265 Scopus citations

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 Ab deposits. These results demonstrate that BM-MSCs are a potential new therapeutic agent for AD.

Original languageEnglish
Pages (from-to)329-343
Number of pages15
JournalStem Cells
Volume28
Issue number2
DOIs
StatePublished - Feb 2010

Keywords

  • Alternatively activated microglia
  • Alzheimer's disease model
  • Amyloid-β; transplantation
  • Bone marrow-derived mesenchymal stem cell

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