Mesenchymal stem cells as treatment for behavioral deficits and neuropathology in the 5xFAD mouse model of Alzheimer’s disease

Jessica J. Matchynski-Franks, Colleen Pappas, Julien Rossignol, Tiffany Reinke, Kyle Fink, Andrew Crane, Alison Twite, Steven A. Lowrance, Cheng Song, Gary L. Dunbar

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Alzheimer’s disease (AD) is characterized by a progressive loss of memory and other cognitive disturbances. The neuropathology of AD includes the major hallmarks of toxic amyloid-β oligomer accumulation and neurofibrillary tangles, as well as increased oxidative stress, cholinergic dysfunction, synapse loss, changes in endogenous neurotrophic factors, and overall degeneration of the brain. Adult mesenchymal stem cells (MSCs) offer the potential for a readily available treatment that would be long lasting, have low likelihood of rejection, and could target a variety of pathological deficits. MSCs have been shown to be effective in alleviating symptoms in some transgenic models of AD, but the optimal location for transplanting MSCs has yet to be determined. In the present study, the behavioral effects of transplantation of MSCs into the lateral ventricles, the hippocampus, or both of these regions were compared in the 5xFAD mouse model of AD. The results indicate that MSC transplants effectively reduce learning deficits in the 5xFAD mouse model and demonstrate a clear impact of MSCs on the levels of Aβ42 in the brains of 5xFAD mice. Overall, these findings support the hypothesis that MSCs may be a viable treatment for AD, especially when injected into the lateral ventricles.

Original languageEnglish (US)
Pages (from-to)687-703
Number of pages17
JournalCell Transplantation
Volume25
Issue number4
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Keywords

  • Alzheimer’s disease (AD)
  • Amyloid-β protein precursor
  • Inflammation mesenchymal stem cells (MSCs)

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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  • Cite this

    Matchynski-Franks, J. J., Pappas, C., Rossignol, J., Reinke, T., Fink, K., Crane, A., Twite, A., Lowrance, S. A., Song, C., & Dunbar, G. L. (2016). Mesenchymal stem cells as treatment for behavioral deficits and neuropathology in the 5xFAD mouse model of Alzheimer’s disease. Cell Transplantation, 25(4), 687-703. https://doi.org/10.3727/096368916X690818