Copyright ©The Author(s) 2019.
World J Stem Cells. Aug 26, 2019; 11(8): 535-547
Published online Aug 26, 2019. doi: 10.4252/wjsc.v11.i8.535
Table 1 Summary of hepatocyte-like cells differentiation protocols
Ref.EB / monolayerProtocol features
In vitro functional assaysIn vivo assay
Endoderm inductionHepatic specification and maturation
Cai et al[18], 2007MonolayerActivin A, ITSFGF4, BMP2, HGF, OSM, DexALB, Glycogen, ICG, LDL, CYP450Yes
Hay et al[19], 2008MonolayerActivin A, Wnt3aSerum, DMSO, Insulin, HGF, OSMUrea, Gluconeogenesis, AFPYes
Agarwal et al[24], 2008MonolayerActivin A, low serumFGF4, HGF, OSM, DexALB, Glycogen, ICGYes
Basma et al[7], 2009EB/monolayerActivin A, bFGFFGF, DMSO, DexALB, Urea, AAT, CYP450Yes
Song et al[20], 2009MonolayerActivin AFGF4, BMP2, HGF, KGF, OSM, DexALB, Urea, Glycogen, CYP450No
Si-Tayeb et al[21], 2010MonolayerActivin ABMP4 FGF2, HGF, OSMGlycogen, LDL, oil red O storage, ICG, UreaYes
Sullivan et al[22], 2010MonolayerActivin A, Wnt3aβ-ME, DMSO, Insulin, HGF, OSMCYP450, Fibrinogen, Fibronectin, Transthyretin, AFPNo
Touboul et al[23], 2010MonolayerActivin A, FGF2, BMP4, LY294002FGF10, RA, SB431542, FGF4, HGF, EGFGlycogen, CYP450, ICG, LDLYes
Borowiak et al[35], 2009MonolayerActivin A, Wnt3a, HGFOSM, Dex, ITSCYP450, Urea, LDL, GlycogenYes
Ogawa et al[34], 2013EB/monolayerBMP4, Activin A, Wnt3aFGF10, bFGF, BMP4, HGF, OSM, Dex, cAMPICG, Glycogen, ALB, CYP450No
Siller et al[37], 2015MonolayerCHIR99021DMSO, dihexa, DexALB, Glycogen, ICG, CYP450No
Table 2 Summary of transplantation studies using hepatocyte-like cells
Ref.Animal modelRouteProliferative stimulusType and number of cellsDonor / recipient (% engrafted)Donor / recipient (% repopulated)Time post-transplantation
Agarwal et al[24], 2008NOD-SCID micePortal veinCCl4-injured106 hES-DEs< 1%NA28 d
Basma et al[7], 2009NOD-SCID miceSpleenRetrorsine and partial hepatectomy1 × 106 hES-HLCsNANA21 d
Liu et al[77], 2011NSG miceTail veindimethylnitrosamine -injured0.1 - 2 × 106 hiPSC- multistage hepatic cells2%–17%8%–15%56 d
Asgari et al[76], 2013Normal mouseTail veinCCl4-injured1 × 106 hiPSC- HLCs2 ± 0.7%NA35 d
Carpentier et al[73], 2014MUP-uPA/ SCID/Bg miceSpleenNA4 × 106 hiPSC-HLCs1%-7%< 1 to up to 20%100 d
Song et al[20], 2015Immunocompetent miceIntraperitoneal cavityNA4.4×105 hiPSC-HLCs in capsulesNANA24 d
Nagamoto et al[74], 2015uPA/SCID miceSpleenNA1 × 106 Ad-FNK-transduced hiPSC-HLCsNANA28 d
Nagamoto et al[78], 2016MicehiPS-HLC sheet transplantation2/3 partial hepatectomy and CCl4-injured8 × 105 hiPSC-HLCsNANA14 d