Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer's Disease.
Jung Yeon LimJung Eun LeeSoon A ParkSang In ParkJung-Min YonJeong-Ah ParkSin-Soo JeunSeung Joon KimHong Jun LeeSung Won KimSeung Ho YangPublished in: Cells (2022)
The aim of this study was to validate the use of human brain organoids (hBOs) to investigate the therapeutic potential and mechanism of human-neural-crest-derived nasal turbinate stem cells (hNTSCs) in models of Alzheimer's disease (AD). We generated hBOs from human induced pluripotent stem cells, investigated their characteristics according to neuronal markers and electrophysiological features, and then evaluated the protective effect of hNTSCs against amyloid-β peptide (Aβ 1-42 ) neurotoxic activity in vitro in hBOs and in vivo in a mouse model of AD. Treatment of hBOs with Aβ 1-42 induced neuronal cell death concomitant with decreased expression of neuronal markers, which was suppressed by hNTSCs cocultured under Aβ 1-42 exposure. Cytokine array showed a significantly decreased level of osteopontin (OPN) in hBOs with hNTSC coculture compared with hBOs only in the presence of Aβ 1-42 . Silencing OPN via siRNA suppressed Aβ-induced neuronal cell death in cell culture. Notably, compared with PBS, hNTSC transplantation significantly enhanced performance on the Morris water maze, with reduced levels of OPN after transplantation in a mouse model of AD. These findings reveal that hBO models are useful to evaluate the therapeutic effect and mechanism of stem cells for application in treating AD.
Keyphrases
- induced pluripotent stem cells
- stem cells
- endothelial cells
- cell death
- mouse model
- high glucose
- cell therapy
- cerebral ischemia
- poor prognosis
- gene expression
- high resolution
- mesenchymal stem cells
- genome wide
- long non coding rna
- mass spectrometry
- blood brain barrier
- drug induced
- bone marrow
- single molecule
- chronic rhinosinusitis
- binding protein