Neurobiology of Aging
Volume 33, Issue 3 , Pages 588-602, March 2012

Human umbilical cord blood-derived mesenchymal stem cells improve neuropathology and cognitive impairment in an Alzheimer's disease mouse model through modulation of neuroinflammation

  • Hyun Ju Lee

      Affiliations

    • Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea
    • Department of Physiology, Cell and Matrix Research, Institute, BSEI, World, Class University Program, School of Medicine, Kyungpook National University, Daegu, Korea
    • ,
  • Jong Kil Lee

      Affiliations

    • Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea
    • Department of Laboratory Animal Medicine, Cell and Matrix Research Institute, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea
    • ,
  • Hyun Lee

      Affiliations

    • Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea
    • Department of Physiology, Cell and Matrix Research, Institute, BSEI, World, Class University Program, School of Medicine, Kyungpook National University, Daegu, Korea
    • ,
  • Janet E. Carter

      Affiliations

    • Department of Mental Health Sciences, Royal Free and University College Medical School, University College London, London, UK
    • ,
  • Jong Wook Chang

      Affiliations

    • Biomedical Research Institute, MEDIPOST Co., Ltd., Republic of Korea
    • ,
  • Wonil Oh

      Affiliations

    • Biomedical Research Institute, MEDIPOST Co., Ltd., Republic of Korea
    • ,
  • Yoon Sun Yang

      Affiliations

    • Biomedical Research Institute, MEDIPOST Co., Ltd., Republic of Korea
    • ,
  • Jun-Gyo Suh

      Affiliations

    • Department of Medical Genetics, College of Medicine, Hallym University, Chuncheon, Korea
    • ,
  • Byoung-Hee Lee

      Affiliations

    • Division of Biological Resources Coordination, National Institue of Biological Resources, Incheon, Korea
    • ,
  • Hee Kyung Jin

      Affiliations

    • Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea
    • Department of Laboratory Animal Medicine, Cell and Matrix Research Institute, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea
    • Corresponding Author InformationCorresponding authors at: Kyungpook National University, Department of Physiology, School of Medicine, 101 Dongindong 2 Ga, Jung-Gu, Daegu 700-422, Republic of Korea; College of Veterinary Medicine, Kyungpook National University, Sankyuk 3-dong, Buk-gu, Daegu 702-701, Republic of Korea. Tel.: +82 53 420 4815, 82 53 950 5966; fax: +82 53 424 3349, 82 53 950 5955
    • ,
  • Jae-sung Bae

      Affiliations

    • Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea
    • Department of Physiology, Cell and Matrix Research, Institute, BSEI, World, Class University Program, School of Medicine, Kyungpook National University, Daegu, Korea
    • Corresponding Author InformationCorresponding authors at: Kyungpook National University, Department of Physiology, School of Medicine, 101 Dongindong 2 Ga, Jung-Gu, Daegu 700-422, Republic of Korea; College of Veterinary Medicine, Kyungpook National University, Sankyuk 3-dong, Buk-gu, Daegu 702-701, Republic of Korea. Tel.: +82 53 420 4815, 82 53 950 5966; fax: +82 53 424 3349, 82 53 950 5955

Received 1 October 2009; received in revised form 26 March 2010; accepted 31 March 2010. published online 17 May 2010.

Abstract 

Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) have a potential therapeutic role in the treatment of neurological disorders, but their current clinical usage and mechanism of action has yet to be ascertained in Alzheimer's disease (AD). Here we report that hUCB-MSC transplantation into amyloid precursor protein (APP) and presenilin1 (PS1) double-transgenic mice significantly improved spatial learning and memory decline. Furthermore, amyloid-β peptide (Aβ) deposition, β-secretase 1 (BACE-1) levels, and tau hyperphosphorylation were dramatically reduced in hUCB-MSC transplanted APP/PS1 mice. Interestingly, these effects were associated with reversal of disease-associated microglial neuroinflammation, as evidenced by decreased microglia-induced proinflammatory cytokines, elevated alternatively activated microglia, and increased anti-inflammatory cytokines. These findings lead us to suggest that hUCB-MSC produced their sustained neuroprotective effect by inducing a feed-forward loop involving alternative activation of microglial neuroinflammation, thereby ameliorating disease pathophysiology and reversing the cognitive decline associated with Aβ deposition in AD mice.

Keywords:  Alzheimer's disease , Human umbilical cord blood-derived mesenchymal stem cell , Amyloid-β , microglia , Spatial learning and memory , Microglial neuroinflammation

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PII: S0197-4580(10)00157-0

doi:10.1016/j.neurobiolaging.2010.03.024

Neurobiology of Aging
Volume 33, Issue 3 , Pages 588-602, March 2012

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