이현주 (경북대학교 의과대학) | 한빛사논문 > 한빛사

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이현주Hyun Ju Lee

경북대학교 의과대학

Neurobiol. Aging, Volume 33, Issue 3, March 2012, Pages 588-602 | https://doi.org/10.1016/j.neurobiolaging.2010.03.024 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^a,b, Jong Kil Lee^a,c, Hyun Lee^a,b, Janet E. Carter^d, Jong Wook Chang^e, Wonil Oh^e, Yoon Sun Yang^e, Jun-Gyo Suh^f, Byoung-Hee Lee^g, Hee Kyung Jin^a,c,*, Jae-sung Bae^a,b,*

^a Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, Korea
^b Department of Physiology, Cell and Matrix Research, Institute, BSEI, World, Class University Program, School of Medicine, Kyungpook National University, Daegu, Korea
^c Department of Laboratory Animal Medicine, Cell and Matrix Research Institute, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea
^d Department of Mental Health Sciences, Royal Free and University College Medical School, University College London, London, UK
^e Biomedical Research Institute, MEDIPOST Co., Ltd., Republic of Korea
^f Department of Medical Genetics, College of Medicine, Hallym University, Chuncheon, Korea
^g Division of Biological Resources Coordination, National Institue of Biological Resources, Incheon, Korea

^*Corresponding authors : Hee Kyung Jin, Jae-sung Bae

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

논문정보

형식Research article
게재일2012년 03월 (BRIC 등록일 2019-04-11)
연구진국내(교신)+국외 연구진
분야 의약학 > 신경의학
피인용횟수120회 이상 인용된 논문

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