LSD1 Inhibition Enhances the Immunogenicity of Mesenchymal Stromal Cells by Eliciting a dsRNA Stress Response
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals and Ethics
2.2. Cell Lines and Reagents
2.3. Bioinformatics Analysis
2.4. Generation of Primary Bone Marrow (BM)-Derived MSCs
2.5. Identification of the TC Maximum Tolerated Dose (MTD) and Subsequent Treatments
2.6. RNA Extraction
2.7. Assessment of dsRNA via Confocal Micropscopy
2.8. Antigen Presentation Assay
2.9. Cytokine Quantification
2.10. Monitoring Peptide: MHC Complex Stability
2.11. Assessing ROS Production in Response to TC Treatment
2.12. Treatment with IFNγ and IDO-1 Quantification
2.13. Design of the Prophylactic Vaccination Study
2.14. Statistical Analysis
3. Results
3.1. TC-Treated MSCs Exhibit a Significant Increase in H2-Kb Expression
3.2. Bioinformatics Analysis Predicts Induced Type-I IFN Signaling and Antigen Presentation in Response to TC Treatment
3.3. MSCs Express dsRNA and Their Cognate Sensing Elements in Response to TC Treatment
3.4. TC-Mediated LSD1 Inhibition Improves MSC Antigen Presentation through Cell Surface MHC:Peptide Complex Stabilization
3.5. IFNγ Treatment Does Not Synergise with TC at Enhancing Antigen Presentation
3.6. TC-Mediated LSD1 Inhibition Enhances the Anti-Tumoral Property of MSCs
3.7. TC Treatment of Human-Derived UC-MSCs Triggers Similar Effects
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mardani, F.; Saad, W.; El-Hachem, N.; Bikorimana, J.-P.; Kurdi, M.; Shammaa, R.; Talbot, S.; Rafei, M. LSD1 Inhibition Enhances the Immunogenicity of Mesenchymal Stromal Cells by Eliciting a dsRNA Stress Response. Cells 2022, 11, 1816. https://doi.org/10.3390/cells11111816
Mardani F, Saad W, El-Hachem N, Bikorimana J-P, Kurdi M, Shammaa R, Talbot S, Rafei M. LSD1 Inhibition Enhances the Immunogenicity of Mesenchymal Stromal Cells by Eliciting a dsRNA Stress Response. Cells. 2022; 11(11):1816. https://doi.org/10.3390/cells11111816
Chicago/Turabian StyleMardani, Fatemeh, Wael Saad, Nehme El-Hachem, Jean-Pierre Bikorimana, Mazen Kurdi, Riam Shammaa, Sebastien Talbot, and Moutih Rafei. 2022. "LSD1 Inhibition Enhances the Immunogenicity of Mesenchymal Stromal Cells by Eliciting a dsRNA Stress Response" Cells 11, no. 11: 1816. https://doi.org/10.3390/cells11111816