Functional Recovery of Alzheimer’s Disease Using Stem Cells from Human Exfoliated Deciduous Tooth-Derived Conditioned Medium
Alzheimer's disease (AD), a progressive neurodegenerative disease, is characterized by deterioration of cognitive function accompanying with deposition of β-amyloid (Aβ) peptides. Aβ peptides are liberated from larger transmembrane amyloid precursor proteins (APP) and generate Aβ42/Aβ40 peptides. These aberrant Aβ peptides form amyloid plaques induce M1-type pro-inflammatory microglia, releasing high levels of cytokines, glutamate, reactive oxygen species, and nitric oxide (NO). This oxidative stress accelerates generation of 3-nitrotyrosine in neuron and consequently suppresses the catecholamine synthesis and depresses neuro-synaptic transmission. Inhibition of the neurotoxic factor production may be a novel AD treatment. We have reported strong immunosuppressive activities of serum free conditioned medium derived from Stem Cells from Human Exfoliated Deciduous Tooth (SHED-CM).
Purpose
In this study, we examined the therapeutic benefits of SHED-CM, Bone marrow mesenchymal stem cells (BMMSC)-CM and skin fibroblast (Fibro)-CM for treatment of the Aβ peptide injected mouse AD-like model.
Materials and Methods
Mouse AD-like model was generated by the i.c.v. injection of oligomerized 5μg of Aβ1-40, or Aβ40–1 was into the 9-week-old ICR mice brain. Twenty-four hours after the i.c.v. injection, a total of 50μl of various type CM, were administered to each mice via the olfactory pathway. The therapeutic effects were evaluated by the behavioral, biochemical and histological examination. All experiments were performed in accordance with the Guidelines for Animal Experiments of Nagoya University Graduate School of Medicine.
Result
SHED-CM suppressed the expressions of pro-inflammatory cytokines, iNOS and 3-nitrotyrosine and improved cognitive function of the mouse AD-like model.
Conclusion
SHED-CM treatment may provide a significant therapeutic benefits for treating cognitive dysfunction of AD.