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.
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.
Lee
Jong Kil
JK
Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea.
Jin
Hee Kyung
HK
Endo
Shogo
S
Schuchman
Edward H
EH
Carter
Janet E
JE
Bae
Jae-Sung
JS
D000544:Alzheimer Disease / Q000150:complications / Q000276:immunology* / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology / Q000276:immunology* / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics
D016229:Amyloid beta-Peptides; D053764:Presenilin-1