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Table 4 Direct reprogramming of fibroblasts to cardiomyocytes in vivo

From: Heart regeneration for clinical application update 2016: from induced pluripotent stem cells to direct cardiac reprogramming

Reprogramming factors

Gene transduction

Species

Disease model

Comments

References

Gata4, Mef2c, Tbx5 (GMT)

Retrovirus

Mouse

Myocardial infarction (MI)

Injected reprogrammed cells

[2]

Mesp1, Tbx5, Gata4, Nkx2.5, Baf60c (MTGNB)

Using a doxycycline-inducible lentivirus vector

Mouse

MI

Improved survival after myocardial infarction (MI)

Differentiate into cardiomyocytes, smooth muscle cells, and endothelial cells

[10]

Oct4, Sox2, Klf4, c-Myc (OSKM)

(−) Using secondary MEFs harboring doxycycline-inducible transgenes encoding reprogramming factors

Mouse

MI

Improves heart function after MI

Reduce infract area Differentiate into cardiomyocytes, smooth muscle cells, and endothelial cells

[11]

Gata4, Hand2, Mef2c, Tbx5 (GHMT)

Retrovirus

Mouse

MI

Injected virus

2.4~6.5 % (border zone) reduction of 50 % in scar zone

[15]

Gata4, Mef2c, Tbx5 (GMT)

Lentivirus

Mouse

MI

Injected reprogrammed cells

[16]

Gata4, Mef2c, Tbx5 (GMT)

Retrovirus

Mouse

MI

Injected virus

Almost 35 % of iCMs in the border/infarct area

Improvement 10 % in ejection fraction

[38]

Gata4, Mef2c, Tbx5 (GMT) 3F-2A system

Polycistronic vectors (retrovirus)

Mouse

MI

Injected virus

1~3 % (border zone)

[31]

miR-1, miR-133, miR-208, miR-499

microRNA

Mouse

MI

Added JAK inhibitor

~1 % (border zone)

[18]

GMT and Vegf (GMT/VEGF)

Lentivirus

Rat

MI

Injected virus

Improvement in ejection fraction fourfold greater in GMT/VEGF vs GMT only

[40]