Human adipose tissue-derived mesenchymal stem cells improve cognitive function and physical activity in ageing mice

J Neurosci Res. 2013 May;91(5):660-70. doi: 10.1002/jnr.23182. Epub 2013 Feb 13.


Brain ageing leads to atrophy and degeneration of the cholinergic nervous system, resulting in profound neurobehavioral and cognitive dysfunction from decreased acetylcholine biosynthesis and reduced secretion of growth and neurotrophic factors. Human adipose tissue-derived mesenchymal stem cells (ADMSCs) were intravenously (1 × 10(6) cells) or intracerebroventricularly (4 × 10(5) cells) transplanted into the brains of 18-month-old mice once or four times at 2-week intervals. Transplantation of ADMSCs improved both locomotor activity and cognitive function in the aged animals, in parallel with recovery of acetylcholine levels in brain tissues. Transplanted cells differentiated into neurons and, in part, into astrocytes and produced choline acetyltransferase proteins. Transplantation of ADMSCs restored microtubule-associated protein 2 in brain tissue and enhanced Trk B expression and the concentrations of brain-derived neurotrophic factor and nerve growth factor. These results indicate that human ADMSCs differentiate into neural cells in the brain microenvironment and can restore physical and cognitive functions of aged mice not only by increasing acetylcholine synthesis but also by restoring neuronal integrity that may be mediated by growth/neurotrophic factors. © 2013 Wiley Periodicals, Inc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Adipose Tissue / cytology*
  • Aging / physiology*
  • Animals
  • Avoidance Learning / physiology
  • Brain / metabolism
  • Brain / pathology
  • Cell Count
  • Cell Differentiation / physiology
  • Choline O-Acetyltransferase / metabolism
  • Cognition Disorders / etiology
  • Cognition Disorders / physiopathology
  • Cognition Disorders / surgery*
  • Disease Models, Animal
  • Gene Expression Regulation / physiology
  • Humans
  • Male
  • Maze Learning / physiology
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Mice, Inbred ICR
  • Motor Activity / physiology*
  • Nerve Tissue Proteins / metabolism
  • Time Factors


  • Nerve Tissue Proteins
  • Choline O-Acetyltransferase
  • Acetylcholine