The preventive and therapeutic effects of intravenous human adipose-derived stem cells in Alzheimer's disease mice

PLoS One. 2012;7(9):e45757. doi: 10.1371/journal.pone.0045757. Epub 2012 Sep 26.

Abstract

Alzheimer's disease (AD) is characterized by the accumulation of amyloid plaques and neurofibrillary tangles accompanied by cognitive dysfunction. The aim of the present study was to elucidate preventive and therapeutic potential of stem cells for AD. Among stem cells, autologous human adipose-derived stem cells (hASCs) elicit no immune rejection responses, tumorigenesis, or ethical problems. We found that intravenously transplanted hASCs passed through the BBB and migrated into the brain. The learning, memory and pathology in an AD mouse model (Tg2576) mice greatly improved for at least 4 months after intravenous injection of hASC. The number of amyloid plaques and Aβ levels decreased significantly in the brains of hASC-injected Tg mice compared to those of Tg-sham mice. Here, we first report that intravenously or intracerebrally transplanted hASCs significantly rescues memory deficit and neuropathology, in the brains of Tg mice by up-regulating IL-10 and VEGF and be a possible use for the prevention and treatment of AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Alzheimer Disease / metabolism*
  • Amyloidogenic Proteins / metabolism
  • Animals
  • Brain / metabolism
  • Cell- and Tissue-Based Therapy / methods*
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation*
  • Humans
  • Injections, Intravenous
  • Interleukin-10 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Fluorescence / methods
  • Time Factors
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Amyloidogenic Proteins
  • Vascular Endothelial Growth Factor A
  • Interleukin-10

Grant support

This research was supported by the Conversing Research Center Program through the National Research Foundation of Korea (NRF) (2011K000678), Mid-career Researcher Program through NRF grant funded by the MEST (20110027566), and a grant (2011K000270) from Brain Research Center of the 21st Century Frontier Research Program, Science and Technology, the Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.