Direct Reprograming to Regenerate Myocardium and Repair Its Pacemaker and Conduction System
Abstract
:1. Introduction
2. Direct Reprogramming for Cardiac Regeneration
2.1. Further Optimizing the TF Cocktail
2.2. Use of Small Molecules to Improve Reprogramming
2.3. Epigenetic Factors and RNA Splicing in iCM Generation
2.4. Direct Reprogramming of Human Fibroblasts
3. Reprogramming to Regenerate the CCS
4. Vector Systems Employed in Direct Reprogramming
5. Future Perspectives
6. Conclusions
Acknowledgments
Conflicts of Interest
Abbreviations
TFs | Transcription factors |
CMs | Cardiac myocytes |
iCMs | induced cardiac myocytes |
Micro RNAs | miRNAs |
MCFs | Mouse cardiac fibroblasts |
MEFs | Mouse embryonic fibroblasts |
TTFs | Tail tip fibroblasts |
GMT | Gata4, Mef2c, Tbx5 |
iAMs | induced atrial myocytes |
iVMs | induced ventricular myocytes |
iPMs | induced pacemaker myocytes |
HCFs | Human cardiac fibroblasts |
CCS | cardiac conduction system |
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Reprogramming Factors | Weeks Post MI | Ejection Fraction | Stroke Volume | Scar Area (%) | References |
---|---|---|---|---|---|
G/M/T vs. dsRed group | 12 w | ~32% vs. 22% | ~42 mL/min vs. 30 mL/min | ~18% vs. 40% | [19] |
G/M/T/H vs. GFP group | 12 w | ~58% vs. 30% | ~55 µL vs. 40 µL | ~18% vs. 40% | [21] |
MGT vs. G/M/T | 8 w | ~38% vs. 24% | ND | ~18% vs. 28% * | [20] |
Reprogramming Factors | Cell Type | Reprogramming Read-Out | Reprogramming Efficiency | Beating Cells | References |
---|---|---|---|---|---|
Gata4, Hand2, Tbx5, Myocardin, miR-1, miR-133 | Human neonatal FFs, adult CFs and DFs | cTNT | 13% | + (Rare) | [45] |
GMT, Mesp1, Myocardin | Human CFs and DFs | Multiple cardiac gene expression, sarcomeric organization structure and calcium oscillations | 6% | - | [46] |
GMT-Mesp1 or GMT, miR-133a | Mouse & Human CFs | a-actinin protein, c-TnT calcium oscillations | 10% (mouse) & 8% (human) | + | [47] |
GMT, Hand2, Myocardin or GMT, miR-590 | Porcine & Human CFs | cTNT | 5% | + | [48] |
SeV-GMT/H | Human CFs | cTNT | 15% | + | [49] |
GMT, ESRRG, MESP1, Myocardin, ZFPM2 | Human ESC derived fibroblasts, neonatal and skin fibroblasts | cTNT | 5% | - | [50] |
GMT, ESRRG, MESP1, Myocardin, ZFPM2, TGFβ inhibitor, Wnt inhibitor | Adult HCF cell line | cTNT | 12% | + | [51] |
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Adepu, S.; Oosterwerff, E.F.J.; Christoffels, V.M.; Boink, G.J.J. Direct Reprograming to Regenerate Myocardium and Repair Its Pacemaker and Conduction System. Medicines 2018, 5, 48. https://doi.org/10.3390/medicines5020048
Adepu S, Oosterwerff EFJ, Christoffels VM, Boink GJJ. Direct Reprograming to Regenerate Myocardium and Repair Its Pacemaker and Conduction System. Medicines. 2018; 5(2):48. https://doi.org/10.3390/medicines5020048
Chicago/Turabian StyleAdepu, Saritha, Erik F. J. Oosterwerff, Vincent M. Christoffels, and Gerard J. J. Boink. 2018. "Direct Reprograming to Regenerate Myocardium and Repair Its Pacemaker and Conduction System" Medicines 5, no. 2: 48. https://doi.org/10.3390/medicines5020048
APA StyleAdepu, S., Oosterwerff, E. F. J., Christoffels, V. M., & Boink, G. J. J. (2018). Direct Reprograming to Regenerate Myocardium and Repair Its Pacemaker and Conduction System. Medicines, 5(2), 48. https://doi.org/10.3390/medicines5020048