Table 2 Direct/partial reprogramming of mouse/rat fibroblasts to cardiomyocytes in vitro

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]