Application of stem cells in the precise diagnosis and treatment of liver diseases

Table 2 Liver organoids generated from human pluripotent stem cells

Organoid types	Stem cells	Biomarkers	Characteristics	Ref.
Vascularized mLOs	hPSCs	HNF1B, HNF4A, albumin, CEBPA, CYP	The mLOs was superior to 2D Hep for HPC maturation; mLOs comprise hepatic- and non-parenchymal cells; mLOs with enhanced structural complexity and functionality	Chi et al[112]
Liver organoids	hPSCs	AFP, albumin, HNF4α, A1AT, KRT19, KRT7, albumin	The hPSC-LOs with various liver cell types highly simulated DENV infection and screened for antivirals	Li et al[69]
Liver organoids	hiPSCs	Albumin, HNF4α, KRT7, KRT19, CK7	The in situ formation of hiPSC-LOs were achieved in microporous array chips; the hiPSC-LOs were competent for evaluating the efficacy of semaglutide for NAFLD	You et al[221]
Liver bud organoids (hLBOs)	hPSCs	STAB2, LYVE1, CD32, CD36, FCGR2B	The vascularized hLBOs contain hepatic and endothelial subpopulations that show key organ-specific functional features, and can restore coagulation factor deficiencies	Saiki et al[98]
Liver bud organoids (hLBOs)	hiPSCs	Albumin, CK18, HNF4α, AFP	The hiPSC-derived hLBOs were competent for whole body in vivo cell tracking and the resultant cell therapy development	Ashmore-Harris et al[119]
Liver bud organoids (hLBOs)	hPSCs	TBX3, ADRA1B, HNF4α, WT1, ADRA1B, LHX2, CD144, CD31	The strategy fulfilled the mass production and batch validation of self-organizing hLBOs with in vitro functions and in vivo therapeutic potential from hPSCs	Takebe et al[118]
Hepatocyte organoids	hiPSCs	Albumin, ASGR1, ASGR2, A1AT, AFP, SERPINA1	HiPSCs were transduced with adeno-associated virus vectors and the hepatocyte organoids enhanced the translation of gene therapies	Berreur et al[125]
Hepatostellate organoids	hiPSCs	Albumin, TTR, TDO2, COL1A1, TIMP1, KRT17, TACSTD2	The hepatostellate organoids were derived from hiPSCs with dyskerin 1 mutation, and would benefit the studies upon telomere dysfunction–induced liver disease	Choi et al[128]

mLO: Multi-lineage liver organoids; hLBOs: Human liver bud organoids; hPSCs: Human pluripotent stem cells; hiPSCs: Human induced pluripotent stem cells; HNF1B: Hepatocyte nuclear factor 1 beta; HNF4A: Hepatocyte nuclear factor 4 alpha; CEBPA: CCAAT/enhancer binding protein alpha; CYP: Cytochrome P450; AFP: Alpha-fetoprotein; A1AT: Alpha-1-antitrypsin; KRT19: Keratin 19; KRT7: Keratin 7; CK7: Cytokeratin 7; STAB2: Stabilin 2; LYVE1: Lymphatic vessel endothelial hyaluronan receptor 1; FCGR2B: Fc gamma receptor IIb; CK18: Cytokeratin 18; TBX3: T-box transcription factor 3; ADRA1B: Alpha-1B adrenergic receptor; WT1: Wilms tumor 1; LHX2: LIM homeobox 2; ASGR1: Asialoglycoprotein receptor 1; ASGR2: Asialoglycoprotein receptor 2; SERPINA1: Serpin family a member 1; TTR: Transthyretin; TDO2: Tryptophan 2,3-dioxygenase; COL1A1: Collagen type I alpha 1 chain; TIMP1: Tissue inhibitor of metalloproteinases 1; KRT17: Keratin 17; TACSTD2: Tumor-associated calcium signal transducer 2; 2D Hep: 2D Hepatocytes; HPC: Hepatic progenitor cells; hPSC-LOs: Human pluripotent stem cell-derived liver organoids; DENV: Dengue virus; hiPSC-LOs: Human induced pluripotent stem cell-derived liver organoids; NAFLD: Non-alcoholic fatty liver disease.