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A brief summary of vascularized liver organoids
| Generation method | Cell types at the generation stage | Vascularization method | Vessel characteristics | Perfusion | Ref. |
|---|---|---|---|---|---|
| Self-organized (condensation on Matrigel bed) | hiPSC-derived hepatic endoderm, HUVECs, MSCs | Spontaneous (mixture of EGM and HCM) | CD31＋ EC network ( |
(13, 14, 66-68) | |
| Human fetal liver cells, HUVECs, MSCs | Spontaneous (EGM) | HUVEC network ( |
(63) | ||
| PHHs, LSECs, MSCs | Spontaneous (mixture of LSEC growth medium and HGM) | CD31＋ EC ( |
- | (64) | |
| hiPSC-derived hepatic endoderm/ECs/STM cells or HUVECs, MSCs | Spontaneous (mixture of EGM and HCM) | EC sprouting ( |
(16) | ||
| hiPSC-derived hepatocytes/ECs/MSCs or human aortic ECs, dental-pulp MSCs | Spontaneous (mixture of EGM and HCM) | CD31 and VE-cadherin IF ( |
- | (69) | |
| UCMSC-derived hepatocytes/LSECs/HSCs | Spontaneous | CD31 IF ( |
- | (65) | |
| Self-organized (embedding in liver extracellular matrix and cultured in microfluidic device) | Induced hepatocytes/HUVECs | Spontaneous (interstitial flow) | CD31＋ EC network ( |
- | (70) |
| Self-organized (assembled in ultra-low attachment plate) | 3D PHHs, HUVECs | Spontaneous (mixture of EGM and HEM) | None | - | (71) |
| hiPSC-derived hepatocytes, primary human HSCs, primary human cholangiocytes, primary human LSECs or hiPSC-ECs | Spontaneous (40 ng/ml VEGF) | CD31＋ capillary-like structure | - | (72) | |
| Self-organized (assembled in non-tissue culture treated plate) | Human or mouse liver progenitor cells, mouse primary LSECs or HUVECs | Spontaneous (mixture of WME and EGM, 50 ng/ml VEGF, 50 ng/ml bFGF) | CD31, LYVE-1, CD32b IHC ( |
- | (73) |
| Self-organized (assembled using microwell film) | hiPSC-hepatoblast/ECs/MSCs | Spontaneous (40 ng/ml bFGF, 100 ng/ml VEGF) | CD31＋ EC network ( |
(74) | |
| Self-organized (layer-by-layer coating of cells) | PHHs or HepG2 cells, HUVECs, normal human dermal fibroblasts | Spontaneous | CD31+ EC network with lumen ( |
(75) | |
| Self-organized (pulsed overexpression of GATA6 in hPSC) | Genetically modified hiPSCs | Spontaneous | CD31, CD34, CD146＋ EC network ( |
(17, 76) | |
| Bio-printed | PHHs, HUVECs, human lung fibroblasts | Prepatterned (EGM) | CD31＋ EC network ( |
(77) | |
| EA.hy926 (human ECs), HepG2/C3A cells | Prepatterned | CD31＋ vessel with lumen ( |
(78) | ||
| Self-condensed liver organoids derived from PHHs, HUVECs, MSCs | Spontaneous (bFGF, VEGF) | CD31 IF and IHC ( |
(79) | ||
| Microfluidic device (liver sinusoid-like chip) | HepaRG, HUVECs, human HSCs (LX2), human primary macrophages | Prepatterned (EGM, interstitial flow) | VE-cadherin IF ( |
(80) | |
| PHHs, primary human LSECs or HUMECs, human HSCs (LX2), human KCs (THP-1) | Prepatterned (interstitial flow) | VE-cadherin IF ( |
(81) | ||
| Microfluidic device (AngioChip) | Primary rat hepatocytes or hESC-derived hepatocytes,HUVECs, MSCs | Prepatterned (EGM, interstitial flow) | CD31 IF ( |
(82) | |
| Re-seeding in decellularized liver | Human fetal liver cells, HUVECs | Prepatterned | vWF and eNOS IF ( |
(83) |
hiPSC: human induced pluripotent stem cell, HUVEC: human umbilical vein endothelial cell, MSC: mesenchymal stem cell, EC: endothelial cell, STM: septum transversum mesenchyme, UCMSC: umbilical cord-derived mesenchymal stem cell, LSEC: liver sinusoidal endothelial cell, HSC: hepatic stellate cell, IF: immunofluorescence staining, IHC: immunohistochemistry, VE-cadherin: vascular endothelial cadherin, LYVE-1: lymphatic vessel endothelial hyaluronan receptor 1, FVIII: Factor VIII, vWF: von-Willebrand factor, αSMA: alpha-smooth muscle actin, eNOS: endothelial nitric oxide synthase, SEM: scanning electron microscopy, TEM: transmission electron microscopy, EGM: endothelial cell growth medium, HCM: hepatocyte culture medium, HEM: hepatocyte expansion medium, HGM: hepatocyte growth medium, VEGF: vascular endothelial growth factor, WME: Wiliam’s E medium, bFGF: basic fibroblast growth factor.