International Journal of Stem Cells : eISSN 2005-5447

Table. 1.

Table. 1.

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 (in vitro); CD31+ vasculature connected to host vessels (after transplantation); blood and dextran perfusion (after transplantation) In vivo (13, 14, 66-68)
Human fetal liver cells, HUVECs, MSCs Spontaneous (EGM) HUVEC network (in vitro and after transplantation); dextran perfusion (after transplantation) In vivo (63)
PHHs, LSECs, MSCs Spontaneous (mixture of LSEC growth medium and HGM) CD31+ EC (in vitro) - (64)
hiPSC-derived hepatic endoderm/ECs/STM cells or HUVECs, MSCs Spontaneous (mixture of EGM and HCM) EC sprouting (in vitro); iPSC-EC-derived vasculature connected to host vessels (after transplantation); blood and dextran perfusion (after transplantation) In vivo (16)
hiPSC-derived hepatocytes/ECs/MSCs or human aortic ECs, dental-pulp MSCs Spontaneous (mixture of EGM and HCM) CD31 and VE-cadherin IF (in vitro) - (69)
UCMSC-derived hepatocytes/LSECs/HSCs Spontaneous CD31 IF (in vitro) - (65)
Self-organized (embedding in liver extracellular matrix and cultured in microfluidic device) Induced hepatocytes/HUVECs Spontaneous (interstitial flow) CD31+ EC network (in vitro); decreased active caspase 3 in organoids cultured with fluid flow - (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 (in vitro); LYVE-1 and CD32b IHC (after transplantation) - (73)
Self-organized (assembled using microwell film) hiPSC-hepatoblast/ECs/MSCs Spontaneous (40 ng/ml bFGF, 100 ng/ml VEGF) CD31+ EC network (in vitro); VE-cadherin, FVIII, and vWF IF (after transplantation); FVIII secretion (in vitro and after transplantation) (74)
Self-organized (layer-by-layer coating of cells) PHHs or HepG2 cells, HUVECs, normal human dermal fibroblasts Spontaneous CD31+ EC network with lumen (in vitro); quantification of vessel length and branching points (in vitro); blood perfusion (after transplantation); CD31, vWF, and CD34 IF (after transplantation); aSMA+ pericyte-like cells covering vessel (after transplantation) In vivo (75)
Self-organized (pulsed overexpression of GATA6 in hPSC) Genetically modified hiPSCs Spontaneous CD31, CD34, CD146+ EC network (in vitro); quantification of vessel length and branching points (in vitro); single-cell RNA-sequencing (EC markers including PDGFB, NOTCH1, ANGPT2, TIE1, DLL4, KDR, CDH5 and ERG); blood perfusion (after transplantation); CD31+ vasculature connected to host vessels (after transplantation) In vivo (17, 76)
Bio-printed PHHs, HUVECs, human lung fibroblasts Prepatterned (EGM) CD31+ EC network (in vitro) (77)
EA.hy926 (human ECs), HepG2/C3A cells Prepatterned CD31+ vessel with lumen (in vitro) (78)
Self-condensed liver organoids derived from PHHs, HUVECs, MSCs Spontaneous (bFGF, VEGF) CD31 IF and IHC (in vitro), CD31 IHC (after transplantation) (79)
Microfluidic device (liver sinusoid-like chip) HepaRG, HUVECs, human HSCs (LX2), human primary macrophages Prepatterned (EGM, interstitial flow) VE-cadherin IF (in vitro) In vitro (microfluidic chip) (80)
PHHs, primary human LSECs or HUMECs, human HSCs (LX2), human KCs (THP-1) Prepatterned (interstitial flow) VE-cadherin IF (in vitro), SEM (LSEC fenestrae, in vitro), fluorescent albumin perfusion and permeability analysis (in vitro) In vitro (microfluidic chip) (81)
Microfluidic device (AngioChip) Primary rat hepatocytes or hESC-derived hepatocytes,HUVECs, MSCs Prepatterned (EGM, interstitial flow) CD31 IF (in vitro), FITC perfusion (in vitro), immune cell (THP-1 and RAW 267 macrophage) perfusion (in vitro) In vitro (microfluidic chip) (82)
Re-seeding in decellularized liver Human fetal liver cells, HUVECs Prepatterned vWF and eNOS IF (in vitro), dextran perfusion (in vitro), TEM (vascular lumen, in vitro) In vitro (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.

International Journal of Stem Cells 2023;16:1-15
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