Protein-Induced Pluripotent Stem Cells Ameliorate Cognitive Dysfunction and Reduce Aβ Deposition in a Mouse Model of Alzheimer's Disease

Stem Cells Transl Med. 2017 Jan;6(1):293-305. doi: 10.5966/sctm.2016-0081. Epub 2016 Aug 15.

Abstract

Transplantation of stem cells into the brain attenuates functional deficits in the central nervous system via cell replacement, the release of specific neurotransmitters, and the production of neurotrophic factors. To identify patient-specific and safe stem cells for treating Alzheimer's disease (AD), we generated induced pluripotent stem cells (iPSCs) derived from mouse skin fibroblasts by treating protein extracts of embryonic stem cells. These reprogrammed cells were pluripotent but nontumorigenic. Here, we report that protein-iPSCs differentiated into glial cells and decreased plaque depositions in the 5XFAD transgenic AD mouse model. We also found that transplanted protein-iPSCs mitigated the cognitive dysfunction observed in these mice. Proteomic analysis revealed that oligodendrocyte-related genes were upregulated in brains injected with protein-iPSCs, providing new insights into the potential function of protein-iPSCs. Taken together, our data indicate that protein-iPSCs might be a promising therapeutic approach for AD. Stem Cells Translational Medicine 2017;6:293-305.

Keywords: 5XFAD mice; Alzheimer's disease; Oligodendrocyte; Protein-iPSC; Proteomic analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / physiopathology*
  • Alzheimer Disease / therapy*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Behavior, Animal
  • Brain / pathology
  • Cell Differentiation
  • Cognitive Dysfunction / complications
  • Cognitive Dysfunction / therapy*
  • Disease Models, Animal
  • Induced Pluripotent Stem Cells / transplantation*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurons / pathology
  • Oligodendroglia / metabolism
  • Plaque, Amyloid / pathology
  • Proteome / metabolism
  • Stem Cell Transplantation
  • Transferrin / metabolism
  • Up-Regulation / genetics

Substances

  • Amyloid beta-Peptides
  • Proteome
  • Transferrin