Open AccessIntracerebral 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
Author(s) -
Lee Jong Kil,
Jin Hee Kyung,
Endo Shogo,
Schuchman Edward H.,
Carter Janet E.,
Bae Jaesung
Publication year - 2010
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.277
Subject(s) - mesenchymal stem cell , transplantation , biology , presenilin , microglia , bone marrow , immune system , hyperphosphorylation , cancer research , alzheimer's disease , immunology , pathology , inflammation , medicine , microbiology and biotechnology , disease , kinase
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. S TEM C ELLS 2010;28:329–343