Stem cells for liver tissue repair: Current knowledge and perspectives

Table 2 Representative studies investigating in vitro and/or in vivo hepatocyte differentiation of HSCs

Cell source	In vitrodifferentiation	In vivodifferentiation	References
Mouse BM	ND	Host: irradiated FAH-/- mice Injury: NTBC withdrawal TRP: 10 to 1000 cells; retroorbital plexus Cell characterization: β-gal+, Alb+, DPPIV+, e-cadherin+, FISH Y+, liver function, FAH activity Repopulation rate: 30%-50% βgal+ cells	Lagasse et al[73]
Mouse BM	ND	Host: irradiated CD45.1+ mice Injury: hepatect or anti-Fas Ab treatment TRP: 106 cells; vein Cell characterization: CK8+, CK18+, CK19+, CD45.2+, FISH Y+, PCR Bcl-2+ Repopulation rate: up to 0.05%-0.8% with anti-Fas Ab treatment	Mallet et al[74]
Human UCB&BM	ND	Host: irradiated NOD/SCID mice ± HGF Injury: CCl4 TRP: 2000 to 105 cells; vein Cell characterization: Alb+, CD45-, human alu+, CK19+, Alb mRNA+, serum Alb+ Repopulation rate: < 1%	Wang et al[77]
Human UCB&PB	ND	Host: irradiated NOD/SCID mice Injury: CCl4 TRP: 2 to 6 × 105 CD34+ cells; tail vein Cell characterization: CD45+, Alb+, α1-AT+, hum DNA+, hum Alb mRNA+&prot+ Repopulation rate: ≤ 0.01% hum Alb mRNA in mice vs human liver	Kollet et al[70]
Mouse BM	Cocktail: co-culture with damaged liver tissue Characterization: RT-PCR (8), ICC (10), FISH Alb mRNA	Host: mice ± irradiation Injury: CCl4 TRP: 105 cells; tail vein Cell characterization: Alb+, FISH Y+, E-cadh+, PKH26+, serum liver function Repopulation rate: up to 7.6% at 2 d Fusion: FISH X-Y: -	Jang et al[69]
Mouse BM	ND	Host: mice ± irradiation ± rhG-CSF Injury: partial hepatect or CCl4 TRP: 5 × 103 selected cells or 5 × 105 MNCs; spleen Cell characterization: no co-eGFP/DPPIV staining, PCR eGFP- Repopulation rate: 0/6.9 × 107 host hepatocytes	Cantz et al[65]

α1-AT: Alpha-1-antitrypsin; Ab: Antibody, Alb: Albumin; β-gal: β-galactosidase; BM: Bone marrow; CCl₄: Carbon tetrachloride; CK: Cytokeratin; d: Days; dexa: Dexamethasone; DPPIV: Dipeptidyl peptidase IV; eGFP: Enhanced green fluorescent protein; FAH: Fumarylacetoacetate hydrolase; hepatect: Hepatectomy; HGF: Hepatocyte growth factor; hum: Human; MNCs: Mononuclear cells; ND: Not documented; NTBC: 2-2nitro-4-trifluoromethylbezoyle-1,3-cyclohexanedione; PB: Peripheral blood; UCB: Umbilical cord blood; E-cadh: E-cadherin; rhG-CSF: Recombinant human Granulocyte-Colony Stimulating Factor; TRP: Transplantation. Amounts of analyzed markers are provided between brackets.