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§

Authors

  • Jong Kil Lee,

    1. Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea
    2. Department of Laboratory Animal Medicine, Cell and Matrix Research Institute, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea
    3. Department of Physiology, Cell and Matrix Research Institute and World Class University Program, School of Medicine and Brain Korea 21, Kyungpook National University, Daegu, Korea
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  • Hee Kyung Jin,

    Corresponding author
    1. Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea
    2. Department of Laboratory Animal Medicine, Cell and Matrix Research Institute, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea
    • College of Veterinary Medicine, Kyungpook National University, 1,370 Sankyuk-dong, Buk-gu, Daegu, 702-701, South Korea
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    • Telephone: +82 53 950 5966; Fax: +82 53 950 5955

  • Shogo Endo,

    1. Unit for Molecular Neurobiology of Learning and Memory, Okinawa Institute of Science and Technology, Uruma, Okinawa, Japan
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  • Edward H. Schuchman,

    1. Departments of Genetics and Genomic Sciences and Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York, U.S.
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  • Janet E. Carter,

    1. Department of Mental Health Sciences, Royal Free and University College Medical School, University College London, London, U.K.
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  • Jae-sung Bae

    Corresponding author
    1. Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea
    2. Department of Physiology, Cell and Matrix Research Institute and World Class University Program, School of Medicine and Brain Korea 21, Kyungpook National University, Daegu, Korea
    • School of Medicine and Brain Korea 21, Kyungpook National University, 101 Dongindong 2Ga, Jung-Gu, Daegu 700-422, South Korea
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    • Telephone: +82 53 420 4815; Fax: +82 53 424 3349


  • Author contributions: H.K.J., J.S.B.: conception and design; H.K.J., J.K.L.: provision of study material and collection of data; H.K.J., J.K.L., S.E., J.S.B.: data analysis and interpretation; H.K.J., J.S.B.: financial support; J.K.L., E.H.S., J.E.C., J.S.B. manuscript writing; H.K.J., E.H.S and J.S.B.: final approval.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • First published online in STEM CELLSEXPRESS January 28, 2010.

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. STEM CELLS 2010;28:329–343

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