Table 1.
Methods for cardiomyocyte differentiation from human pluripotent stem cells, ranked by purity of yields
| hPSC expansion platform | Cardiomyocyte differentiation platform | Biomolecules | Purity | Scalability | Comments | Reference |
|---|---|---|---|---|---|---|
| Monolayer on feeders or Matrigel |
Monolayer |
Activin A, BMP4, VEGF, SCF, WNT3a |
24% (Nkx 2.5) |
+ |
|
[25] |
| |
|
BMP2, 5% FBS |
41.6% (cTnT) |
+ |
|
[30] |
| |
|
Activin A, BMP4 |
51% (MHC) |
+ |
|
[10] |
| |
|
Activin A, BMP4, DKK1 |
54.2% (cTnT) |
+ |
|
[31] |
| |
|
Activin A, BMP4, FGF2 , VEGF, DKK1 |
57.2% (cTnT) |
+ |
|
[32] |
| |
|
Activin A, BMP4 |
60% (α-actinin) |
+ |
|
[33] |
| |
|
Activin A, BMP4, IWP-4 or IWR-1 |
60.6% (MHC) |
+ |
|
[34] |
| |
|
Activin A, BMP4, FGF2, Noggin, BMS-189453, DKK1 |
73.0% (cTnT) |
+ |
|
[35] |
| |
|
BMP4, ascorbic acid, CHIR99021, IWR-1 |
80% (cTnT) |
+ |
|
[36] |
| |
|
Activin A, BMP4, FGF2 |
80% (cTnT) |
+ |
|
[27] |
| |
|
Activin A, BMP4, VEGF |
85.4% (cTnT) |
+ |
|
[37] |
| |
|
CHIR99021, IWP-2/IWP-4 |
88.3% (cTnT) |
+ |
|
[38] |
| |
|
FBS |
90% (cTnT) |
+ |
|
[39] |
| |
|
CHIR99021, BIO, KY02111, XAV939 |
97.7% (cTnT) |
+ |
|
[40] |
| |
Embyoid bodies |
Activin A, FGF2 |
23.6% (beating EBs) |
++ |
Forced aggregation |
[41] |
| |
|
Normoxic |
48.3% (beating EBs) |
++ |
Micropatterned; controlled bioreactor |
[42] |
| |
|
BMP4 |
95.8% (beating EBs) |
+ |
Replated after 4 days |
[43] |
| |
|
Ascorbic acid |
6.94% (cTnT) |
+ |
Replated after 5 days |
[44] |
| |
|
BMP4, IWP-1 |
15.6% (cTnT) |
+ |
Replated after 4 days |
[45] |
| |
|
SB203580 |
16% (MHC) |
++ |
|
[28] |
| |
|
SB203580 |
22.0% (MHC) |
++ |
|
[46] |
| |
|
BMP2, 5-azacytidine |
23.7% (cTnT) |
+ |
Replated after 6 days |
[47] |
| |
|
SB203580 |
26% (MHC) |
++ |
|
[48] |
| |
|
Activin A, BMP4, FGF2, VEGF, SCF |
26.8% (Nkx 2.5) |
++ |
Forced aggregation |
[24] |
| |
|
Activin A, BMP4, FGF2, VEGF |
27.1% (MHC) |
+ |
Replated after 4 days |
[49] |
| |
|
Activin A, BMP4, FGF2, VEGF, DKK1 |
37.2% (cTnT) |
++ |
|
[50] |
| |
|
WNT3a |
50% (α-actinin) |
+ |
Replated after 6 days |
[51] |
| |
|
BMP2 |
53.3% (cTnT) |
++ |
|
[52] |
| |
|
CHIR99021, IWP-2 |
60% (cTnT) |
++ |
|
Unpublished data |
| |
|
Activin A, BMP4, FGF2, VEGF, DKK1 |
60.2% (cTnI) |
++ |
|
[53] |
| |
|
Activin A, BMP4, FGF2 , VEGF, DKK1 |
82% (cTnT) |
++ |
|
[23] |
| |
|
BMP4,FGF2 |
82.3% (cTnI) |
++ |
Forced aggregation |
[54] |
| |
|
Activin A, BMP4, FGF2, VEGF,DKK1 |
91.6% (cTnT) |
++ |
Dissociated EBs |
[55] |
| |
Microcarriers |
SB203580 |
20% (MHC) |
+++ |
|
[28] |
| Cell aggregate |
Monolayer |
Activin A, BMP4, FGF2 |
80% (cTnT) |
+ |
|
[27] |
| |
Embryoid bodies |
Activin A, BMP4, FGF2, VEGF, DKK1 |
27% (cTnT) |
+++ |
|
[56] |
| |
|
BMP4 |
36.9% (Nkx 2.5) |
+ |
hESC encapsulation |
[57] |
| |
|
Activin A, BMP4, FGF2, VEGF, IWR-1 |
80% (cTnT) |
+++ |
Controlled bioreactor |
[27] |
| |
Microcarriers |
No data |
|
|
|
|
| Microcarriers | Microcarriers | CHIR99021, IWP-2 | 67% (cTnT) | +++ | Unpublished data |
BMP, bone morphogenetic protein; cTnI, cardiac troponin I; cTnT, cardiac troponin T; EB, embryoid body; FBS, fetal bovine serum; FGF, fibroblast growth factor; hESC, human embryonic stem cell; hPSC, human pluripotent stem cell; MHC, myosin heavy chain; SCF, stem cell factor; VEGF, vascular endothelial growth factor.