Modeling of LMNA-Related Dilated Cardiomyopathy Using Human Induced Pluripotent Stem Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Characteristics
2.2. hiPSC Generation, Culture and Characterization
2.3. Cardiomyocyte Differentiation
2.4. Genotyping
2.5. Immunofluorescence and Confocal Microscopy
2.6. Transmission Electron Microscopy
2.7. Immunoblotting
2.8. Micro Electrode Array (MEA) Electrophysiology
2.9. Hypoxic Stress Induction on MEA
2.10. Calcium Imaging
2.11. Teratoma Assay
3. Results
3.1. Generation and Characterization of hiPSC Lines
3.2. Characterization of Cardiac Differentiation and Lamina Structure
3.3. DCM-CMs Exhibit Increased Arrhythmias on MEA
3.4. Increased Sarcomere Disorganization after Ischemic Stress in DCM-CMs
3.5. DCM-CMs Show Increased Cellular Stress
3.6. Hypoxia Reduces Beat Rate of Cardiac Aggregates
3.7. DCM-CMs Show Impaired Calcium Dynamics
4. Discussion
5. Conclusions
5.1. Clinical Significance
5.2. Study Limitations
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Shah, D.; Virtanen, L.; Prajapati, C.; Kiamehr, M.; Gullmets, J.; West, G.; Kreutzer, J.; Pekkanen-Mattila, M.; Heliö, T.; Kallio, P.; et al. Modeling of LMNA-Related Dilated Cardiomyopathy Using Human Induced Pluripotent Stem Cells. Cells 2019, 8, 594. https://doi.org/10.3390/cells8060594
Shah D, Virtanen L, Prajapati C, Kiamehr M, Gullmets J, West G, Kreutzer J, Pekkanen-Mattila M, Heliö T, Kallio P, et al. Modeling of LMNA-Related Dilated Cardiomyopathy Using Human Induced Pluripotent Stem Cells. Cells. 2019; 8(6):594. https://doi.org/10.3390/cells8060594
Chicago/Turabian StyleShah, Disheet, Laura Virtanen, Chandra Prajapati, Mostafa Kiamehr, Josef Gullmets, Gun West, Joose Kreutzer, Mari Pekkanen-Mattila, Tiina Heliö, Pasi Kallio, and et al. 2019. "Modeling of LMNA-Related Dilated Cardiomyopathy Using Human Induced Pluripotent Stem Cells" Cells 8, no. 6: 594. https://doi.org/10.3390/cells8060594
APA StyleShah, D., Virtanen, L., Prajapati, C., Kiamehr, M., Gullmets, J., West, G., Kreutzer, J., Pekkanen-Mattila, M., Heliö, T., Kallio, P., Taimen, P., & Aalto-Setälä, K. (2019). Modeling of LMNA-Related Dilated Cardiomyopathy Using Human Induced Pluripotent Stem Cells. Cells, 8(6), 594. https://doi.org/10.3390/cells8060594