Table 2. Direct endothelial reprogramming with lineage-specific factors.
| Reprogrammed cell name | Source cell type | Key factors (chemicals) | Delivery method | Culture condition | Culture duration | Reference |
|---|---|---|---|---|---|---|
| rAC-VEC | Human amniotic fluid-derived cell | ETV2, FLI1, and ERG1 (SB431542) | Lentiviral infection | EM: SB431542, EC supplement, and Heparin | 28 days | Ginsberg et al., Cell (2012)20) |
| iEC | Mouse skin and tail-tip fibroblast | Etv2, Foxo1, Klf2, Tal1 and Lmo2 | Lentiviral infection | EBM-2 | 12 days | Han et al., Circulation (2014)24) |
| iEC* | Human neonatal dermal fibroblast | (Poly I:C) | Chemical stimulation | Activation of innate immunity: Poly I:C | 7 days + 7 days + 14 days and more | Sayed et al., Circulation (2015)37) |
| Transdifferentiation medium I: bFGF, VEGF, and BMP4 | ||||||
| Transdifferentiation medium II: EGM-2, bFGF, VEGF, BMP4, and 8-Br-cAMP | ||||||
| After sorting: EGM-2 and SB431542 | ||||||
| ETVEC | Human adult fibroblast | ETV2 (VEGF and bFGF) | Lentiviral infection | EGM-2, VEGF, and bFGF | 25 days (beyond 50 days) | Morita et al., Proc Natl Acad Sci U S A (2015)25) |
| iEC | Human neonatal fibroblast | ETV2, FLI1, GATA2, and KLF4 (BMP4, VEGF, bFGF, and SB431542) | Lentiviral infection | Differentiation medium: BMP4, VEGF, and bFGF | 3 days + 25 days | Wong and Cooke, J Tissue Eng (2016)26) |
| EC growth medium: EGM-2 MV and SB431542 | ||||||
| rEC (early vs. late) | Human dermal fibroblast | ETV2 (VEGFA and VPA) | Lentiviral infection | Early rEC: EGM-2 and VEGFA | 7 days for early rEC and 3 months for late rEC | Lee et al., Circ Res (2017)27) |
| Late rEC: EGM-2, temporal treatment of VPA, and VEGFA | ||||||
| EiEC | Human adipose-derived stem cell and human umbilical mesenchymal stem cells | ETV2 (SB431542, VEGF, bFGF, and EGF) | Lentiviral infection | EIM: Insulin, ascorbic acid, Heparin, VEGF, bFGF, EGF, SB431542, CHIR99021 and BMP4 | 10 days (up to 2 months) | Cheng et al., Stem Cell Res Ther (2018)28) |
| EMM: SB431542, VEGF, bFGF, and EGF | ||||||
| iEC | Human embryonic lung fibroblast | DKK3 (VEGF) | Adenoviral infection | EGM-2 and VEGF | 10 days or more | Chen et al., Arterioscler Thromb Vasc Biol (2019)29) |
| Fsk-iEC | Human fibroblast and UCB-MSC | ETV2 (forskolin) | Lentiviral or retroviral infection | EGM-2 and Forskolin | 14 days | Kim et al., Mol Ther (2020)30) |
| iVEC | Human dermal fibroblast | ETV2 | Retroviral infection | EGM-2 MV | N/A | Bersini et al., Elife (2020)31) |
| iEC | Human adult dermal fibroblast | ETV2, KLF2 and TAL1 with siTWIST1 (rosiglitazone) | Lentiviral infection | 1st stage: EGM-2 MV and rosiglitazone | 4 weeks + 2 weeks | Han et al., Biomaterials (2021)32) |
| 2nd stage: EGM-2 MV |
EBM-2 = Endothelial Cell Growth Basal Medium-2; EC = endothelial cell; EGM-2 MV = Microvascular Endothelial Cell Growth Medium-2; EiEC = ETV2-induced endothelial cell; EIM = endothelial induction medium; EM = endothelial growth media; EMM = endothelial maintenance medium; Fsk = forskolin; iEC = induced endothelial cell; iEnd cell = induced endothelial cell; iVEC = induced vascular endothelial cell; N/A = not applicable; PiPSC-EC = partial-induced pluripotent stem cell-derived endothelial cell; rAC-VEC = reprogrammed amniotic fluid-derived cell-vascular endothelial cell; rEC = reprogrammed endothelial cell; siTWIST = small interfering RNA of TWIST1; UCB-MSC = umbilical cord blood-derived mesenchymal stem cell; VEGF = vascular endothelial growth factor; VPA = valproic acid.
*Chemically driven direct reprogramming towards ECs.