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. 2010 Feb;28(2):329-43. doi: 10.1002/stem.277.

Abstract

Alzheimer's disease (AD) is characterized by the deposition of amyloid-beta peptide (Abeta) 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 beta-peptide (Abeta) deposition. Interestingly, these effects were associated with restoration of defective microglial function, as evidenced by increased Abeta-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 Abeta deposits. These results demonstrate that BM-MSCs are a potential new therapeutic agent for AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / immunology*
  • Alzheimer Disease / therapy*
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Blotting, Western
  • Bone Marrow Cells / cytology*
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Maze Learning
  • Memory Disorders / etiology
  • Memory Disorders / immunology*
  • Memory Disorders / therapy*
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mice
  • Mice, Transgenic
  • Presenilin-1 / genetics

Substances

  • Amyloid beta-Peptides
  • Presenilin-1