Table 1.
In vitro and in vivo efficiencies of GMT-based reprogramming strategies.
| Reprogramming strategy | Fibroblast origin | Efficiency | Study | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Core factors | Species | Additional factors | Embryonic | Dermal | Cardiac | Cardiac marker expression | Spontaneously beating cells | Reprogramming in vivo | Authors |
| GMT | Mouse | None | X | X | 4% cTnT/αMHC-GFP+ (CFs); 2.5% cTnT/αMHC-GFP+ (TTFs) | Rare | Rare detection of reprogrammed cells in hearts | Ieda et al., 2010 | |
| Polycistronic delivery | X | 3–7% αMHC-GFP+ | Not discussed | ~1% GFP/α-actinin+ following GMT+GFP injection into infarct | Inagawa et al., 2012 | ||||
| +Thymosin β4 | X | N/A | N/A | GMT vs. DsRed | Qian et al., 2012 | ||||
| EF = 25% vs. 16%; Fibrosis reduced 75% | |||||||||
| None | X | X | 35% GFP+ Tnnt2-Cre/Rosa26 mTmG reporter TTFs | Not detected | Cardiac gene expression detected in reprogrammed cells | Chen et al., 2012 | |||
| +MyoCD, SRF, MESP1, and SMARCD3 | X | 2.4% αMHC-GFP+ | Not detected | N/A | Christoforou et al., 2013 | ||||
| +miR-133 | X | X | 20% α-actinin+, 12% cTnT+ (MEFs); 3.5% cTnT+ (TTFs) | ~7-fold enhanced by miR-133 vs. GMT alone | N/A | Muraoka et al., 2014 | |||
| Polycistronic delivery | X | X | 3–4% cTnT/αMHC-GFP+ (neonatal CFs) | ~10-fold enhanced by polycistronic delivery vs. previous studies | N/A | Wang et al., 2015a | |||
| +FGF2/FGF10/VEGF (FFV) | X | X | 1% cTnT/αMHC-GFP+ | ~20-fold enhanced by FFV vs. GMT alone | N/A | Yamakawa et al., 2015 | |||
| Polycistronic delivery | X | N/A | N/A | Polycistronic GMT vs. DsRed | Ma et al., 2015 | ||||
| EF = ~38% vs. 17%; FS = ~18.4% vs. ~7.5%; Fibrotic area = ~20% vs. ~40% | |||||||||
| Polycistronic delivery +shBmi1 | X | X | X | 22% cTnT/αMHC-GFP+ (neonatal CFs) | 2-fold enhanced by shBmi1 | N/A | Zhou et al., 2016 | ||
| Polycistronic delivery +TGF-β/WNT inhibition | X | 16% cTnT/αMHC-GFP+ (neonatal CFs) | ~40% of cells seeded | GMT ± inhibitors vs. DsRed | Mohamed et al., 2017 | ||||
| EF = ~35% vs. 20%; Fibrotic area = ~15% vs. ~39% | |||||||||
| Polycistronic delivery +shPbtb1 | X | 45% cTnT/αMHC-GFP+ | Not discussed | N/A | Liu et al., 2017 | ||||
| Polycistronic Sendai viral delivery | X | X | X | 10% cTnT+ | ~50% of MEFs seeded; ~10% of total cells | Polycistronic GMT vs. GFP | Miyamoto et al., 2018 | ||
| EF = ~35% vs. ~25%; FS = ~15% vs. ~10%; Reduced fibrosis | |||||||||
| Polycistronic delivery +shBcor | X | X | ~9–16% cTnT/αMHC-GFP+ (CFs); ~1.2% cTnT/αMHC-GFP+ (MEFs) | Not discussed | N/A | Zhou et al., 2018 | |||
| Alternate MEF2C isoforms | X | X | X | 5% cTnT/αMHC-GFP+ (MEFs); 4% cTnT/αMHC-GFP+ (CFs); 1.25% cTnT/αMHC-GFP+ (TTFs) | Not discussed | N/A | Wang et al., 2020b | ||
| Polycistronic delivery +shBeclin1 | X | X | X | 6% cTnT+ (MEFs); 20% cTnT+ (CFs); 5% cTnT+ (TTFs) | ~3-fold enhanced by shBeclin1 | Polycistronic GMT ± Beclin±/− vs. DsRed | Wang et al., 2020c | ||
| EF = ~40% vs. ~20%; FS = ~29% vs. ~10%; Fibrotic area = 25% vs. 45% | |||||||||
| Rat | +VEGF | X | X | 7% cTnT+ | Not discussed | GMT ± VEGF vs. GFP | Mathison et al., 2012 | ||
| EF = 63% vs. 48%; Fibrotic area = 12% vs. 24% | |||||||||
| Polycistronic delivery +VEGF | X | 7.5% cTnT+ | Not discussed | GMT ± VEGF vs. GFP; | Mathison et al., 2014 | ||||
| EF = 48% vs. 39%; Fibrosis = 21% vs. 31% | |||||||||
| None | X | 5% cTnT+ | Not discussed | N/A | Singh et al., 2016 | ||||
| +VEGF and adenoviral GMT delivery | X | 6.9% cTnT+ | Not discussed | Ad-GMT±VEGF vs. Ad-Null; | Mathison et al., 2017 | ||||
| EF (Change from baseline); +21% vs. −0.4% | |||||||||
| +HDAC/WNT inhibition and Retinoic Acid | X | 23% cTnT+ | Not detected | N/A | Singh et al., 2020 | ||||