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
Abstract
:1. Background
2. Methods
2.1. Human Lung Tissue Dissociation and Generation of Human Induced Pluripotent Stem Cells (hiPSCs)
2.2. hiPSC Culture
2.3. Generation of hBOs
2.4. Transmission Electron Microscopy (TEM)
2.5. Generation of Aβ Oligomers
2.6. Human-Neural-Crest-Derived Nasal Turbinate Stem Cell (hNTSC) Culture
2.7. Human Neural Stem Cell (hNSC) Culture
Culture and Treatment
2.8. Quantitative RT-PCR
2.9. Cytokine Antibody Array
2.10. ELISA Assay
2.11. Cell Transplantation
2.12. Immunohistofluorescence Staining
2.13. Western Blots
2.14. Behavioral Test
2.15. Quantification and Statistical Analysis
3. Results
3.1. Characteristics of hiPSC-Derived hBOs
3.2. Aβ1–42 Induces Neurotoxic Activity in hBO Culture
3.3. hNTSCs Inhibit Aβ1–42 Neurotoxic Activity in hBO Culture
3.4. Identification of OPN as a Functional Factor for hNTSC-Mediated Neuroprotection against Aβ1–42 Toxicity in hBO Culture
3.5. Suppression of OPN Expression Inhibits Aβ1–42 Neurotoxic Activity in Human Neural Stem Cell (hNSC) Culture
3.6. Transplantation of hNTSCs Suppresses OPN Expression in the Brain of 5× FAD Mice
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Ethical Approval and Consent to Participate
Abbreviations
Aβ1–42 | Amyloid-β peptide |
AD | Alzheimer’s disease |
BO | Brain organoid |
DAPI | 4′,6-Diamidino-2-phenylindole |
DMEM | Dulbecco’s modified eagle medium |
FBS | Fetal bovine serum |
HBSS | Hanks’ balanced salt solution |
iPSC | Induced pluripotent stem cell |
α-MEM | α-Minimum essential medium |
NCSC | Neural crest-derived stem cell |
NSC | Neural stem cell |
NTSCs | Neural crest-derived nasal turbinate stem cells |
PBS | Phosphate-buffered saline |
OPN | Osteopontin |
PFA | Paraformaldehyde |
TUNEL | Terminal deoxynucleotidyl transferase dUTP nick end labeling |
TEM | Transmission electron microscopy |
3D | Three dimensional |
TG | Transgenic |
2D | Two-dimensional |
WT | Wild-type |
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Lim, J.Y.; Lee, J.E.; Park, S.A.; Park, S.I.; Yon, J.-M.; Park, J.-A.; Jeun, S.-S.; Kim, S.J.; Lee, H.J.; Kim, S.W.; et al. 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. Cells 2022, 11, 1029. https://doi.org/10.3390/cells11061029
Lim JY, Lee JE, Park SA, Park SI, Yon J-M, Park J-A, Jeun S-S, Kim SJ, Lee HJ, Kim SW, et al. 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. Cells. 2022; 11(6):1029. https://doi.org/10.3390/cells11061029
Chicago/Turabian StyleLim, Jung Yeon, Jung Eun Lee, Soon A Park, Sang In Park, Jung-Min Yon, Jeong-Ah Park, Sin-Soo Jeun, Seung Joon Kim, Hong Jun Lee, Sung Won Kim, and et al. 2022. "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" Cells 11, no. 6: 1029. https://doi.org/10.3390/cells11061029