Table 1.
hESCs and hiPSCs strategies for human endothelial cell derivation
| Study | Cell line | Induction system | Purification method | Culture milieu | Induction Period (days) | Efficiency | Positive control | In vitro analysis | In vivo analysis | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Medium | Growth factors | Other special factors | EC markers analyzed | Application/functional assessment | ||||||||
| Levenberg et al. [23] | hESCs:H9 | 3D EB formation | PECAM1 (FACS) | EGM-2 | EGM-2 supplements | No | 13–15 | 2% of total cell population | HUVEC | Genes analysis for PECAM1, VE-cad, CD34, Flk-1, Tie-2 Protein analysis for PECAM1, VE-cad, vWF | In vitro Matrigel sprouting assay LDL uptake assay | Transplantation into SCID mice |
| Goldman et al. [24] | hESCs:H9 | 3D EB formation | CD144/KDR (FACS) | knockout DMEM | IL-3, IL-6, G-CSF, Flt-3, SCF | BMP4 | 12 | More than 12% of total cell population | HUVEC |
Genes analysis for CD144, KDR Protein analysis for CD144, KDR, CD31, CD34, vWF |
In vitro Matrigel sprouting assay Migration assay in response to a VEGF gradient | No |
| Kim et al. [25] | hESCs: CHA-3; | 3D EB formation | No | DMEM+F12 (50% respectively) | No | No | 15 | – | No | Genes analysis for PECAM1, Flk-1, Tie-2 Protein analysis for PECAM1, vWF | In vitro Matrigel sprouting assay LDL uptake assay | No |
| Figueiredo et al. [34] | hESCs:H1 | 2D cells-co-culture system | No | 훼-MEM | No | No | 9 | (CD31+) 18.45% of total cell population | – | Protein analysis for CD31, KDR, CD144 | Vascular tube-like structure formation | No |
| Lippmann et al. [35] | hESCs:H9 | 2D cells-co-culture system | No | 7 days unconditioned medium, 6 days EC medium | – | – | 13 | (PECAM-1+) 63% of total cell population | No |
Genes analysis for PECAM1, vWF, VE-cad Protein analysis for PECAM1, vWF, VE-cad |
LDL uptake assay In vitro Matrigel sprouting assay |
No |
| Orlova et al. [37] | hESCs: HES3; HES4 | 2D growth factor-supplemented differentiation system | CD31 (MACS) | mTeSR1 culture medium | VEGF-A; BMP4; Activin A | CHIR; SB431542 | 10 | (VE-Cad/CD31+) 19.9% of total cell population | No | Protein analysis for CD31, VE-cad, vWF | Tube formation assay | Zebrafish xenotransplantation assay |
| Kane et al. [40] | hESCs:SA461; SA121 | 2D growth factor-supplemented differentiation system | No | Large vessel endothelial growth media | Hydrocortisone, EGF, bFGF, heparin | – | 14 | (VE-Cad/CD31+) 57.04% of total cell population |
HUVEC HSVEC HMVEC |
Gene analysis for CD31, Flt-1, KDR, VE-cad, CD34 Protein analysis for CD31, VE-cad; |
NO production assay Tube formation assay |
Transplantation into immunocompromised mice |
| Elcheva, I. et al. [41] | hESCs:H1; H9 | 2D genetic manipulation system | No | mTeSR1 culture medium | – | – | 5 | Not clear | No | Protein analysis for CD31, VE-cad, vWF, CD34, CD73, KDR |
LDL uptake assay Tube formation assay |
No |
| Lindgren et al. [42] | hESCs | Genetic manipulation combined with EB formation | No | DMEM+F12 | VEGF; bFGF2 | – | 7 | Not clear | No |
Gene analysis for CD31, KDR, VE-cad Protein analysis for CD31, KDR, VE-cad |
In vitro Matrigel sprouting assay; | No |
| Adams et al. [31] | hiPSCs | 3D EB formation | VE-cad (MACS) | – | – | Fetal calf serum | 10 | About 18% of total cell population | No |
Gene analysis for CD31, KDR, VE-cad Protein analysis for CD31, KDR, VE-cad, eNOS |
LDL uptake assay In vitro Matrigel sprouting assay |
No |
| Lin et al. [43] | hiPSCs | 3D EB formation with addition of growth factors | KDR (FACS) | EGM2 |
VEGF bFGF |
– | 20 | About 20% of total cell population | No |
Genes analysis for KDR, CD31 Protein analysis for CD31, VE-cad |
LDL uptake assay In vitro Matrigel sprouting assay |
Matrigel plug assay in NOD/SCID mice |
| Choi et al. [50] | hiPSCs | 2D cell-co-culture system | CD34 (MACS) with CD31 (FCAS) | 훼-MEM | – | – | 8 | 2.8%~ 6.0% of total cell population | No | Protein analysis for CD31, KDR, CD49d, CD105, CD144, CD146, vWF, VE-cad | Tube formation assay | No |