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

Table 1 Differentiation of human pluripotent stem cells into hepatic parenchymal and non-parenchymal cells

Liver lineages	Stem cell types	Culture medium	Supplements	Days of induction	Biomarkers	Ref.
Hepatocyte-like cells	hiPSCs	RPMI/B27, KO-DMEM with KSR, IMDM	Activin A, Wnt3a, HGF, OSM, Dex, ITS premix	12 days	AFP, albumin, CK18, HNF4, CYP3A4, CYP7A1	Chen et al[76]
Hepatocyte-like cells	hiPSCs	Hepatocyte culture medium, IMDM, N2/B27	Acitivin A, FGF4, BMP2, HGF, KGF, OSM, Dex	21 days	AFP, albumin, CK8, CK18, CK19, PEPCK, HNF4α, HNF6, CEBPα, GATA4, HEX	Song et al[75]
Hepatocyte cells	GATA6- hiPSCs	StemFit04, IMDM/Ham’s F-12K, N2/B27	L-ascorbic acid, Dex, 2-phosphate, basic fibroblast growth factor, 1-thioglycerol, HGF, nicotinamide, OSM	18 days	Albumin, AAT, AFP, HNF4A, CYP3A4, CYP3A5	Luo et al[126]
Hepatic cells	hESCs	DMEM/F12, KSR, 1640 medium	Activin A, aFGF, basic fibroblast growth factor, FGF4, HGF, BMP2, BMP4, Noggin, OSM, Dex, Su5402	18 days	PEPCK, CYP7A1, CYP3A4, CYP2B6	Cai et al[74]
Hepatocytes	hPSCs	DEI medium A/B, CDM3 medium, CDM5 medium	A8301, FGF2, Acitivin A, BMP4, ATRA, AAP, TTNPB, OSM, insulin, forskolin, SB505124, 8-bromo-cAMP, DAPT, CHIR99021, AA2P, RO4929097, Dex	18 days	Fumarylacetoacetate hydrolase, albumin, HGD	Ang et al[71]
Hepatic stellate cells	hiPSCs	Liver differentiation medium	BMP4, FGF1, FGF3, retinol, palmitic acid	12 days	PDGFRβ, PCHD7, COL1α1	Vallverdú et al[2]
Hepatic stellate cells	hPSCs	DMEM low glucose	BMP4, FGF1, FGF3, retinol, palmitic acid, ITS, Dex	12 days	DES, P75NTR, ALCAM, ACTA2, COL1α1, LRAT, RELN, PCDH7, PDGFRβ	Coll et al[91]
Hepatic stellate cells	hESCs	DMEM/F-12, B27, FBS	Activin A, CHIR99021, BMP4, FGF1, FGF3, Y-27632, palmitic acid, retinol	12 days	PDGFRβ, NCAM1, ALCAM, LRAT, ACTA2, vimentin	Wilhelmsen et al[92]
LSECs	hPSCs	EBM-2 medium, IMDM	BMP4, basic fibroblast growth factor, VEGF-A, CHIR99021, cAMP, GSI, SB431542, ITS-X, ascorbic acid, transferrin	22 days	CD34, PECAM1, VWF, LYVE1, CD14, FCGR2B, CD36, CD54, STAB1, FVIII, STAB2, CLEC1B	Gage et al[97]
LSECs	hPSCs	IMDM, DMEM-F12, StemPro34, FCS	BMP4, Activin A, ascorbic acid, basic fibroblast growth factor, L-685-458, ITS-X, VEGF-A, CHIR99021, transferrin	21 days	FCGR2B, LYVE1, STAB2, F8, CD14, MRC1, CD36, RAMP3, CD32B, FVIII	Gage et al[96]
LSECs	Mouse ESCs	IMEM, EGM2-MV, FBS	Adrenomedullin, SB431542, β-ME, VEGF-A, ITS	20 days	F8, Fcgr2b, Mrc1	Arai et al[100]
Cholangiocytes	hPSCs	RPMI 1640 medium, low glucose DMEM, B27, DMEM/F12, a-MEM	MTG, Acitivin A, CHIR99021, ascorbic acid, basic fibroblast growth factor, BMP4, HGF, EGF, OSM, Dex, RA, Noggin, Y-27632, forskolin	49 days	Albumin, AFP, CFTR, TRPV4, PKD1, PKD2	Ogawa et al[101]
Cholangiocytes	hiPSCs	RPMI, B27, William’s E medium	Acitivin A, FGF2, FGF10, BMP4, Ly294002, SB431542, RA, EGF	26 days	SSTR2, ALP, KRT7, SOX9	Sampaziotis et al[102]
Kupffer cells	hiPSCs	X-VIVO 15 media, PHCM, advanced DMEM	M-CSF, IL-3, streptomycin	4-5 weeks	CD163, CD200R, CD86, IL-6, CSF1, HLA-DRB1, IL-1β	Tasnim et al[106]
Kupffer cells	hESCs; cord blood	DMEM/F12, KSR, IMDM, RPMI 1640	BMP4, basic fibroblast growth factor, Activin A, IL-3, IL-7, M-CSF, TPO, SCF	9-17 days (cord blood); > 90 days (hESCs)	MARCO, CD5 L, TIMD4, VCAM1, CPVL, VSIG4, FOLR2, CD163	Kent et al[99]

LSECs: Liver sinusoidal endothelial cells; hiPSCs: Human induced pluripotent stem cells; hESCs: Human embryonic stem cells; hPSCs: Human pluripotent stem cells; ESCs: Embryonic stem cells; KO-DMEM: Knockout Dulbecco’s modified eagle medium; KSR: Knockout serum replacement; IMDM: Iscove’s modified Dulbecco’s medium; CDM3: Chemically defined medium 3; CDM5: Chemically defined medium 5; FBS: Fetal bovine serum; EBM-2: Endothelial basal medium-2; FCS: Fetal calf serum; IMEM: Iscove’s modified eagle medium; EGM2-MV: Endothelial growth medium-2 microvascular; a-MEM: Minimum essential medium alpha modification; PHCM: Primary hepatocyte culture medium; HGF: Hepatocyte growth factor; OSM: Oncostatin M; Dex: Dexamethasone; ITS: Insulin-transferrin-selenium; FGF4: Fibroblast growth factor 4; BMP2: Bone morphogenetic protein 2; KGF: Keratinocyte growth factor; aFGF: Acidic fibroblast growth factor; BMP4: Bone morphogenetic protein 4; FGF2: Fibroblast growth factor 2; ATRA: All-trans retinoic acid; AAP: Ascorbic acid 2-phosphate; AA2P: Ascorbic acid 2-phosphate; FGF1: Fibroblast growth factor 1; FGF3: Fibroblast growth factor 3; VEGF-A: Vascular endothelial growth factor A; cAMP: Cyclic adenosine monophosphate; GSI: Gamma-secretase inhibitor; ITS-X: Insulin-transferrin-selenium-X; β-ME: Β-mercaptoethanol; EGF: Epidermal growth factor; RA: Retinoic acid; M-CSF: Macrophage colony-stimulating factor; IL-3: Interleukin-3; IL-7: Interleukin-7; TPO: Thrombopoietin; SCF: Stem cell factor; AFP: Alpha-fetoprotein; CK18: Cytokeratin 18; HNF4: Hepatocyte nuclear factor 4; CYP3A4: Cytochrome P450 3A4; CYP7A1: Cytochrome P450 7A1; CK8: Cytokeratin 8; CK19: Cytokeratin 19; PEPCK: Phosphoenolpyruvate carboxykinase; HNF4α: Hepatocyte nuclear factor 4 alpha; HNF6: Hepatocyte nuclear factor 6; CEBPα: CCAAT/enhancer binding protein alpha; AAT: Alpha-1-antitrypsin; HNF4A: Hepatocyte nuclear factor 4 alpha; CYP3A5: Cytochrome P450 3A5; CYP2B6: Cytochrome P450 2B6; HGD: Homogentisate 1,2-dioxygenase; PDGFRβ: Platelet-derived growth factor receptor beta; PCDH7: Protocadherin 7; COL1α1: Collagen type I alpha 1 chain; DES: Desmin; P75NTR: P75 neurotrophin receptor; ALCAM: Activated leukocyte cell adhesion molecule; ACTA2: Actin alpha 2, smooth muscle; LRAT: Lecithin retinol acyltransferase; RELN: Reelin; NCAM1: Neural cell adhesion molecule 1; PECAM1: Platelet endothelial cell adhesion molecule 1; VWF: Von willebrand factor; LYVE1: Lymphatic vessel endothelial hyaluronan receptor 1; FCGR2B: Fc gamma receptor IIb; STAB1: Stabilin 1; FVIII: Factor VIII; STAB2: Stabilin 2; CLEC1B: C-type lectin domain family 1 member B; RAMP3: Receptor activity-modifying protein 3; CFTR: Cystic fibrosis transmembrane conductance regulator; TRPV4: Transient receptor potential vanilloid 4; PKD1: Polycystin 1; PKD2: Polycystin 2; SSTR2: Somatostatin receptor; ALP: Alkaline phosphatase; KRT7: Keratin 7; SOX9: SRY-box transcription factor 9; IL-6: Interleukin-6; CSF1: Colony-stimulating factor 1; HLA-DRB1: Human leukocyte antigen-DRB1; IL-1β: Interleukin-1 beta; MARCO: Macrophage receptor with collagenous structure; TIMD4: T-cell immunoglobulin and mucin domain-containing protein 4; VCAM1: Vascular cell adhesion molecule 1; CPVL: Carboxypeptidase, vitellogenic-like; VSIG4: V-set and immunoglobulin domain-containing protein 4; FOLR2: Folate receptor 2.

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.

Table 3 Clinical trials of liver organoids for liver diseases

NCT No.	Study title	Study status	Condition	Enrollment	Study type	Location
NCT06929845	“Organoid Models of Hepatocellular Carcinoma”	Recruiting	HCC	150	Interventional	Italy
NCT02436564	“In Vitro Models of Liver and Pancreatic Cancer”	Unknown	Cholangiocarcinoma	75	Observational	United Kingdom
NCT05913141	“PDO/PDO-TIL/PDOTS for Drug Screen”	Recruiting	HCC	30	Observational	China
NCT06077591	“Prospective Clinical Validation of Next Generation Sequencing and Patient-Derived Tumor Organoids (PDO) Guided Therapy in Patients with Advanced/ Inoperable Solid Tumors”	Recruiting	HCC	40	Interventional	China
NCT06355700	“Hepatocellular Carcinoma Liver Organoids”	Recruiting	HCC	10	Interventional	Italy
NCT06699524	“Construction of a Recurrence Risk Prediction Model for Liver Resection Based on Drug Sensitivity of Patient-derived Hepatocellular Carcinoma Organoid”	Active not recruiting	HCC	122	Observational	China
NCT06856252	“Human Liver Organoids as a Model to Study the Development of NASH”	Recruiting	NASH	60	Interventional	Italy
NCT06787625	“Development of Organoids From Primary Colorectal Tumors and Synchronous Liver Metastases”	Recruiting	Colorectal cancer	10	Observational	Italy
NCT05932836	“An Organoid-on-chips Technique Based on Biopsy Samples and Its Efficacy in Predicting the Response to HAI in HCC”	Active not recruiting	HCC	165	Observational	China

HCC: Hepatocellular carcinoma; NASH: Non-alcoholic steatohepatitis.

Table 4 Clinical trials of stem cell-based observational and interventional studies for liver diseases

NCT No.	Study title	Cell types	Study status	Condition	Phase	Enrollment	Study type	Location
NCT00953693	“Patient Specific Induced Pluripotency Stem Cells (PSiPS)”	hiPSCs	Completed	Liver insufficiency	N/A	15	Observational	Iran
NCT01591200	“Dose Finding Study to Assess Safety and Efficacy of Stem Cells in Liver Cirrhosis”	MSCs	Completed	Alcoholic liver cirrhosis	Phase 2	40	Interventional	India
NCT01429038	“MSCs After Renal or Liver Transplantation”	MSCs	Completed	Liver failure	Phase 1/2	40	Interventional	Belgium
NCT00655707	“A Phase I/II Safety and Tolerability Dose Escalation Study of Autologous Stem Cells to Patients With Liver Insufficiency”	Adult stem cells	Completed	Liver insufficiency	Phase 1/2	5	Interventional	United Kingdom
NCT02089919	“Cancer Stem Cells Vaccine Therapy in Treating Hepatocellular Cancer Patients”	Cancer stem cells	Completed	HCC	Phase 1/2	40	Interventional	China
NCT00147043	“Adult Stem Cell Therapy in Liver Insufficiency”	Adult stem cells	Completed	Liver cirrhosis	N/A	5	Interventional	United Kingdom
NCT04243681	“Combination of Autologous MSC and HSC Infusion in Patients With Decompensated Cirrhosis”	MSCs + hematopoetic stem cells	Completed	Decompensated liver cirrhosis	Phase 4	5	Interventional	India
NCT01333228	“Evaluate Safety and Efficacy of Autologous Bone Marrow-derived Endothelial Progenitor Cells in Advanced Liver Cirrhosis”	BM-EPCs	Completed	Liver cirrhosis	Phase 1/2	14	Interventional	Spain
NCT05331872	“Umbilical Cord-derived MSC Infusion in the Management of Adult Liver Cirrhosis”	UC-MSCs	Completed	Liver cirrhosis	Phase 1	20	Interventional	Vietnam
NCT00420134	“Improvement of Liver Function in Liver Cirrhosis Patients After Autologous MSC Injection: A Phase I-II Clinical Trial”	Autologous MSCs	Completed	Liver cirrhosis	Phase 1/2	30	Interventional	Iran
NCT01454336	“Transplantation of Autologous MSC in Decompensated Cirrhotic Patients With Pioglitazone”	Autologous MSCs	Completed	Decompensated liver cirrhosis	Phase 1	3	Interventional	Iran
NCT02557724	“Mobilization of MSCs During Liver Transplantation”	MSCs	Completed	Liver failure, HCC	N/A	35	Observational	United States
NCT01875081	“REVIVE (Randomized Exploratory Clinical Trial to Evaluate the Safety and Effectiveness of Stem Cell Product in Alcoholic Liver Cirrhosis Patient)”	Stem cells	Completed	Alcoholic liver cirrhosis	Phase 2	72	Interventional	South Korea
NCT01013194	“Human Fetal Liver Cell Transplantation in Chronic Liver Failure”	Fetal liver cells	Completed	Liver cirrhosis	Phase 1/2	25	Interventional	Italy
NCT02297867	“Clinical Trial Study About Human Adipose-Derived Stem Cells in the Liver Cirrhosis”	ASCs	Completed	Liver cirrhosis	Phase 1	6	Interventional	China
NCT01378182	“Efficacy of In vitro Expanded Bone Marrow Derived Allogeneic MSC Transplantation Via Portal Vein or Hepatic Artery or Peripheral Vein in Patients With Wilson Cirrhosis”	BM-MSCs	Completed	Wilson’s disease	NA	10	Interventional	Turkey
NCT01120925	“Autologous Bone Marrow Derived Stem Cells in Decompensated Cirrhotic Patients”	BM-MSCs	Completed	Decompensated liver cirrhosis	Phase 1/2	30	Interventional	Iran
NCT01220492	“Umbilical Cord MSCs for Patients With Liver Cirrhosis”	UC-MSCs	Completed	Liver cirrhosis	Phase 1/2	266	Interventional	China
NCT01342250	“Human Umbilical Cord MSCs Transplantation for Patients With Decompensated Liver Cirrhosis”	UC-MSCs	Completed	Liver cirrhosis	Phase 1/2	20	Interventional	China
NCT03468699	“Autologous Bone Marrow Mononuclear Stem Cell for Children Suffering From Liver Cirrhosis Due to Biliary Atresia”	BM-MSCs	Completed	Liver fibrosis (biliary atresia)	Phase 2	17	Interventional	Vietnam
NCT04522869	“Umbilical Cord Derived MSC (UC -MSC) Transplantation for Children Suffering From Biliary Atresia”	UC-MSCs	Completed	Primary biliary cirrhosis	Phase 1/2	20	Interventional	Vietnam
NCT01625351	“A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas”	Hematopoetic stem cells	Completed	Hepatic tumor	Phase 1	23	Interventional	United States
NCT00003966	“Defibrotide in Treating Patients With Liver Damage Following Peripheral Stem Cell Transplantation”	Peripheral stem cells	Completed	Veno-occlusive disease	Phase 2	151	Interventional	United States
NCT03132337	“Sinusoidal Obstruction Syndrome for Stem Cell Transplant Patients Biomarker Study”	Stem cells	Completed	Sinusoidal obstruction syndrome	N/A	80	Observational	United States
NCT03963921	“Safety and Tolerability of HepaStem in Patients With Cirrhotic and Pre-cirrhotic NASH Patients”	HepaStem	Completed	NASH	Phase 1/2	23	Interventional	Belgium, Spain
NCT00956891	“Therapeutic Effects of Liver Failure Patients Caused by Chronic Hepatitis B After Autologous MSCs Transplantation”	Autologous MSCs	Completed	Liver failure	N/A	158	Observational	China
NCT02727673	“Relationship Between Circulating Tumor Stem Cells and the Clinical Pathology”	Tumor stem cells	Completed	HCC	N/A	1000	Observational	China
NCT00358501	“Defibrotide for the Treatment of Severe Hepatic Veno-Occlusive Disease in Hematopoetic Stem Cell Transplant Patients”	Hematopoetic stem cells	Completed	Severe hepatic veno-occlusive disease	Phase 3	134	Interventional	United States, Canada
NCT00007813	“Peripheral Stem Cell Transplantation Plus Chemotherapy in Treating Patients With Malignant Solid Tumors”	Peripheral stem cells	Completed	Liver cancer	Phase 1	21	Interventional	United States
NCT04423237	“Risk Factors and Measures to Prevent Liver and Pancreas Complications in Pediatric Patients After HSCT”	Hematopoetic stem cells	Completed	Liver complication	N/A	39	Observational	Italy
NCT03511794	“Effectiveness of the Hepatitis B Vaccine Post-Hematopoietic Stem Cell Transplant”	Hematopoetic stem cells	Completed	Hepatitis B	N/A	52	Observational	United States
NCT01481649	“Risk of Hepatitis B Reactivation After Bone Marrow Transplantation With Prior Hepatitis B Virus (HBV) Exposure”	Stem cells	Completed	Exposure to hepatitis B virus	N/A	69	Observational	China
NCT00002515	“Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Rare Cancer”	Stem cells	Completed	HCC	Phase 2	N/A	Interventional	United States
NCT06892236	“Preparation of IPSC for Cell Gene Editing for the Treatment of AATD”	hiPSCs	Recruiting	Alpha1-antitrypsin deficiency	NA	3	Interventional	Italy
NCT06242405	“Effect of Different Frequencies of Umbilical Cord-MSCs Through Peripheral Vein in Patients with ESLD”	UC-MSCs	Recruiting	End-stage liver disease	NA	92	Interventional	China
NCT06564740	“Stem Cell Applications in Biliary Atresia Patients”	Stem cells	Recruiting	Liver fibrosis (biliary atresia)	NA	64	Interventional	Turkey
NCT06740149	“Efficacy and Safety of BMSCs (CG-BM1) for ACLF Patients”	BM-MSCs	Recruiting	ACLF	Phase 1/2	90	Interventional	China
NCT06904755	“Safety and Effectiveness of MSCs in Blood Purification for the Treatment of Liver Failure”	MSCs	Recruiting	Liver failure	Phase 1	10	Interventional	China
NCT05106972	“Umbilical Cord MSC Transplantation for Decompensated Hepatitis B Cirrhosis”	UC-MSCs	Recruiting	Liver cirrhosis	NA	30	Interventional	China
NCT05985863	“Human Umbilical Cord MSC Transplantation for The Treatment of Acute-on-Chronic Liver Failure”	UC-MSCs	Recruiting	ACLF	Phase 1/2	150	Interventional	China
NCT04689152	“Clinical Trial to Evaluate the Efficacy and Safety of Cellgram-LC Administration in Patients With Alcoholic Cirrhosis”	Cellgram-LC	Recruiting	Alcoholic cirrhosis	Phase 3	200	Interventional	South Korea
NCT03826433	“hUC-MSCs (19#iSCLife®-LC) in the Treatment of Decompensated Hepatitis b Cirrhosis hepatitis b Cirrhosis”	UC-MSCs	Recruiting	Hepatitis B	Phase 1	20	Interventional	China
NCT00382278	“Safety Study of Autologous Stem Cell in Liver Cirrhosis”	Autologous stem cells	Terminated	Liver cirrhosis	Phase 1/2	15	Interventional	Brazil
NCT03860155	“Allogeneic ABCB5-positive Stem Cells for Treatment of Acute-on-Chronic Liver Failure”	Allogeneic stem cells	Terminated	ACLF	Phase 1/2	5	Interventional	Germany
NCT00923052	“The Natural History of Solid Organ Cancer Stem Cells (SOCSC)”	Cancer stem cells	Terminated	Hepatic cancer	N/A	190	Observational	United States

hiPSCs: Human induced pluripotent stem cells; MSCs: Mesenchymal stem/stromal cells; BM-EPCs: Bone marrow-derived endothelial progenitor cells; UC-MSCs: Umbilical cord-derived mesenchymal stem/stromal cells; BM-MSCs: Bone marrow-derived mesenchymal stem/stromal cells; HCC: Hepatocellular carcinoma; NASH: Non-alcoholic steatohepatitis; ACLF: Acute-on-chronic liver failure; N/A: Not Applicable; NA: Not Available.