Therapeutic Potential of Nerve Growth Factor-Modified Hair Follicle Stem Cells Transplantation in a Rat Model of Alzheimer's Disease.

Abstract

BACKGROUND: Alzheimer's disease (AD) is a degenerative condition affecting the central nervous system and is the primary cause of dementia. Current therapies for AD are ineffective. Although brain regeneration via stem cell transplantation has therapeutic potential, suitable sources are limited. Hair follicle stem cells (HFSCs) are multi-potent cells and can differentiate into mesodermal and ectodermal lineages, and proliferate for extended periods. Nerve growth factor (NGF) is a neurotrophin that is vital for neuronal development and survival, and the regulation of apoptosis in neurodegenerative disorders. However, using HFSCs to treat AD has not been extensively investigated. Herein, we evaluated the therapeutic effects of HFSCs and the synergistic effect of NGF and HFSCs on AD. METHODS: A rat model of AD was established by intrahippocampal injection of amyloid β-protein 1-42 (Aβ1-42). After 14 days, HFSCs and HFSCs overexpressing NGF were injected into the hippocampus of AD rats for therapy. The cognitive function of the treated AD rats was tested using the Morris water maze test. Congo red staining, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) were used to detect deposition, as well as soluble Aβ1-40 and Aβ1-42 levels. Additionally, western blotting was used to assess tau protein, the phosphoinositide-3 kinase (PI3K)/protein kinase B/glycogen synthase kinase-3β (Akt/GSK-3β) pathway, and the levels of synapse proteins. RESULTS: HFSCs and HFSCs/NGF transplantation not only significantly reduced Aβ deposition but also inhibited GSK-3β activity and reduced tau protein hyperphosphorylation by stimulating the PI3K/Akt signaling pathway. Moreover, HFSC and HFSC/NGF transplantation led to significant overexpression of the synaptophysin (SYP) and postsynaptic density protein 95 (PSD95) in the hippocampus of AD rats. CONCLUSIONS: HFSCs and NGF-modified HFSCs may become a promising treatment option for AD.