Mesenchymal Stem Cells Could Be Considered as a Candidate for Further Studies in Cell-Based Therapy of Alzheimer's Disease via Targeting the Signaling Pathways.

Abstract

Mesenchymal stem cells (MSCs) are of particular interest because of their potential in regenerative medicine. Stem cell-based therapies cast a new hope for neurodegenerative disease treatment as a regeneration strategy, including treatment for Alzheimer's disease (AD). A multitude of cytokines and factors secreted from MSCs are known to give such multifunctional properties, but associated mechanisms of these factors have yet to be entirely understood. To better understand the in vitro effect of MSCs on a neurodegenerative disorder, we treated primary cortical and hippocampal neural cells with amyloid β (Aβ) as an in vitro cell line model for AD. For this purpose, bone marrow-derived MSCs (BMSCs) were cocultured with Aβ-treated neural cells, collected at day 3, and subjected to absolute telomere length measurement and telomerase activity assay. Next, the gene and protein expression levels of mTOR, p-mTOR, AMPK, p-AMPK, GSK-3β, p-GSK-3β, Wnt3, and β-catenin were investigated. Also, after 3 days of coculture treatment, the supernatant was collected from both groups for cytokine measurement. It was found that telomere length as a biomarker in neurodegenerative disorder as well as telomerase activity had significantly increased in the experimental group, and the presence of IL-6, IL-10, and TGF-β was obviously significant in the cocultured media. Also, BMSCs significantly changed the gene and protein expression of mTOR, AMPK, GSK-3β, and Wnt3/β-catenin signaling pathways components. It was concluded that the mentioned effects of MSCs on neural cells as an in vitro cell line model for AD as a therapeutic agent can be related to the signaling network.