Table 2.
Direct/partial reprogramming of mouse/rat fibroblasts to cardiomyocytes in vitro
| Reprogramming factors | Supplement agents | Species | Starting cell source | Efficiency | Comments | References |
|---|---|---|---|---|---|---|
| Gata4, Mef2c, Tbx5 (GMT) | Mouse | Adult cardiac fibroblasts (CFs) and tail-tip fibroblasts (TTFs) | 20~30 % cTnT+ cells after 1 week | Beating after 4 weeks (CFs) Using retrovirus and lentivirus |
[2] | |
| Oct4, Sox2, Klf4 (, c-Myc) | JAK inhibitor I, BMP4 | Mouse | Mouse embryonic fibroblasts (MEFs) | 40 % cTnT(+) after 18 days | Partial reprogramming Beating after 18 days in cluster Using secondary MEFs harboring doxycycline-inducible transgenes encoding reprogramming factors. |
[8] |
| Oct4 | ALK4/5/7 inhibitor, GSK3 inhibitor, LSD/KDM1 inhibitor, BMP4 | Mouse | MEFs, TTTFs | Make clusters | Partial reprogramming Beating after 20 days Without any evidence of entrance into the pluripotent state Using doxycycline inducible-expression lentivirus-based gene delivery system |
[9] |
| Mesp1, Tbx5, Gata4, Nkx2.5, Baf60c (MTGNB) | BIO, LIF | Mouse | MEFs, CFs | Passage over 20 times, expand more than 1015-fold | Partial reprogramming Using a doxycycline-inducible lentivirus vector |
[10] |
| Oct4, Sox2, Klf4, c-Myc (OSKM) | JAK inhibitor (JI1), BACS (BMP4, Activin A,CHIR99021, and SU5402) | Mouse | MEFs, TTFs | Expanded more than 1010-fold | Partial reprogramming Using secondary MEFs harboring doxycycline-inducible transgenes encoding reprogramming factors |
[11] |
| Gata4, Mef2c, Tbx5 (GMT) | Mouse | CFs and TTFs | 35 % cTnT+ cells | Beating after 4~5 weeks Using retrovirus |
[15] | |
| Gata4, Mef2c, Tbx5 (GMT) | Mouse | CFs and TTFs | 35 % cTnT+ cells | Beating after 4~5 weeks Using lentivirus |
[16] | |
| Myocd, Mef2, Tbx5 (3F-Myocd) | Mouse | MEFs and neonatal CFs | 2.5 % αMHC+ cells | Analysis of ion-channel Using lentivirus |
[17] | |
| miR-1, miR-133, miR-208, miR-499 | JAK inhibitor 1 | Mouse | CFs | 13~28 % αMHC+ cells | Added JAK inhibitor Only micro RNAs |
[18] |
| GMT, Hand2, Nkx2-5 (HNGMT) | Mouse | MEFs, CFs | Almost 5 % the calcium indicator GCaMP(+) cells | Using the induction of calcium oscillation for screening Utilizing an inducible-expression lentivirus-based gene delivery system (lentivirus) |
[19] | |
| GMT, Mesp1, Myocd, Smarcd3 (Baf60c), SRF | Mouse | MEFs | 2.4 % αMHC+ cells | Using lentivirus | [20] | |
| GMT, miR-133 | Mouse | MEFs, CFs | 40~50 % αMHC+ cells (MEFs) | Beating after 10 days Using retrovirus |
[21] | |
| Gata4, Mef2c-MyoD fusion, Tbx5, Hand2 | Mouse | MEFs, TTFs | 10–20 % cTnT(+) cells | Beating after 7 days Using retrovirus |
[22] | |
| Mef2c-P2A-Gata4-T2A-Tbx5 | Mouse | Adult CFs | Tenfold increase in beating iCMs Using polycistronic vectors (retrovirus) |
[23] | ||
| Gata4, Mef2c, Tbx5, Hand2, Nkx2-5 (HNGMT) | TGFβ inhibitor | Mouse | MEFs, CFs | 17 % the calcium indicator GCaMP(+) cells | Beating approximately fivefold compared to 16) Using a doxycycline-inducible lentivirus vector |
[24] |
| Gata4, Mef2c, Tbx5, Hand2 (GHMT) | Akt1 | Mouse | MEFs, CFs, TTFs | 50 % of reprogrammed MEFs beating | Beating after 3 weeks Using retrovirus |
[25] |
| (−) | CHIR99021, RepSox, Forskolin, VPA, Parnate, TTNPB, DZnep | Mouse | MEFs, TTFs | Chemical reprogramming Beating after 20–24 days |
[26] | |
| Gata4, Mef2c, Tbx5, Hand2 (GHMT), miR-1, miR-133 | A83-01 (inhibitor of TGF-β1), Y-27632 (inhibitor of ROCK) | Mouse | MEFs, CFs | 60 % cTnT(+) cells after | Beating 2 weeks Using retrovirus |
[27] |
| Gata4, Mef2c, Tbx5 (Hand2) | FGF2, FGF10, VEGF, IWR-1 | Mouse | MEFs, CFs, TTFs | 10–20 % αMHC(+) cells after 1 week | 1 % Beating after 4 weeks (GMT) 5~9 % Beating after 4 weeks (GHMT) Using retrovirus |
[28] |
| Mef2c, Tbx5 | FGF2, FGF10, VEGF | Mouse | MEFs | 3 % αMHC(+) cells after 1 week | Beating after 4 weeks Using retrovirus |
[28] |