: 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.
SIGNIFICANCE
Alzheimer's disease (AD) leads to cognitive dysfunctions without methods for cure or prevention. Here we demonstrated that transplantation of protein-induced pluripotent stem cells (iPSCs) reduced plaque deposition and restored memory impairment in 5XFAD mice, an AD animal model. Also, the stem cell niche of these mice promotes differentiation of protein-iPSCs to glial cells, especially oligodendrocytes. Comparative analysis of the proteome revealed that oligodendrocyte-related genes, including transferrin, were upregulated in the transplanted stem cell niche and that transferrin enhanced differentiation of protein-iPSCs into oligodendrocytes by promoting its maturation. Therefore, protein-iPSCs may provide potential therapeutic interventions with a glial cell-derived approach for neurodegenerative disorders, including AD.