Table 2.
Summary of recent studies reporting on the functional capabilities of human pluripotent stem cell-derived HLCs
| Reference | Phase I and II enzyme activity | Other comparators used (assay method) | Albumin secretion in media | Other functional activity shown | ||
|---|---|---|---|---|---|---|
| Enzyme | % of hPH comparator (assay method) | % of hPH comparator | Other comparators used | |||
| Cai et al., 2007 [50] | CYP2B6 | ND | hESC (fluorescence) | ND | Huh-7 hepatoma cell line | Glycogen storage, ICG uptake, LDL uptake |
| Ek et al., 2007 [51] | CYP1A1 | 0 (fluorescence) | – | ND | ND | – |
| CYP3A4 | 0 (fluorescence) | – | ||||
| Söderdahl et al., 2007 [52] | GST | 80 (fluorescence) | HepG2 hepatoma cell line (fluorescence) | ND | ND | Glycogen storage |
| Hay et al., 2008 [53] | CYP1A2 | 4 (LC-MS-MS) | hESC (LC-MS-MS) | ND | HLCs assayed with no comparator | Glycogen storage |
| Shiraki et al., 2008 [54] | ND | – | – | ND | – | Glycogen storage |
| Agarwal et al., 2008 [55] | ND | – | – | ND | hESC | Glycogen storage, ICG uptake |
| Moore et al., 2009 [56] | CYP1A2 | ND | hESC-derived HLCs cultured in media with different components (fluorescence) | ND | hESC-derived HLCs cultured in media with different components | ICG uptake |
| Basma et al., 2009 [57] | CYP1A | 30 (fluorescence) | – | 75 | – | – |
| CYP3A | 90 (LC-MS-MS) | |||||
| Song et al., 2009 [58] | CYP2B6 | ND | hiPSC-derived HLCs compared with hESC-derived HLCs (fluorescence) | ND | hiPSC-derived HLCs compared with hESC-derived HLCs | Glycogen storage |
| Duan et al., 2010 [59] | CYP1A2 | 100 (LC-MS-MS) | – | ND | HLCs assayed with no comparator | ICG uptake |
| CYP2C9 | 60 (LC-MS-MS) | – | ||||
| CYP2D6 | 95 (LC-MS-MS) | – | ||||
| CYP3A4 | 90 (LC-MS-MS) | – | ||||
| Touboul et al., 2010 [61] | CYP3A | ND | HLCs assayed with no comparator (bioluminescence) | ND | Thawed foetal hepatocytes | Glycogen storage, ICG uptake, LDL uptake |
| Brolén et al., 2010 [62] | CYP1A, | ND | Spontaneously differentiated hESC-derived HLCs, HepG2 (LC-MS-MS) | ND | – | Glycogen storage, ICG uptake |
| CYP2C, | ||||||
| CYP3A | ||||||
| Ghodsizadeh et al., 2010 [82] | CYP2B6 | ND | hiPSC (fluorescence) | ND | HLCs assayed with no comparator | Glycogen storage, ICG uptake, LDL uptake |
| Liu et al., 2010 [63] | CYP1A2, CYP3A4 | ND | HLCs assayed with no comparator (bioluminescence) | ND | ND | Glycogen storage |
| Si-Tayeb et al., 2010 [65] | ND | – | – | ND | hiPSC-derived HLCs compared with hESC-derived HLCs | Glycogen storage, ICG uptake, LDL uptake |
| Sullivan et al., 2010 [81] | CYP1A2 | – | HLCs assayed with no comparator (bioluminescence) | ND | ND | – |
| CYP3A4 | ||||||
| Rashid et al., 2010 [83] | CYP3A4 | ND | hiPSC (bioluminescence) | ND | hiPSC | Glycogen storage, LDL uptake |
| Zhang et al., 2011 [66] | CYP3A4 | 0.32 (bioluminescence) | hESC-derived HLCs (bioluminescence) | 60 | – | Glycogen storage |
| Bone et al., 2011 [64] | ND | – | – | 22.6 | – | – |
| Yildirimman et al., 2011 [69] | CYP1A2 | 50 (LC-MS-MS) | – | ND | – | – |
| CYP3A4 | 50 (LC-MS-MS) | |||||
| CYP2B6 | 10 (LC-MS-MS) | |||||
| CYP2C9 | 50 (LC-MS-MS) | |||||
| CYP2C19 | 50 (LC-MS-MS) | |||||
| Chen et al., 2012 [67] | CYP3A4 | 100 (bioluminescence) | hiPSC (bioluminescence) | ND | – | Glycogen storage, LDL uptake |
ELISA, enzyme-linked immunosorbent assay; GST, glutathione transferase; ICG, indocyanine green; LC-MS-MS, liquid chromatography with tandem mass spectrometry; LDL, low density lipoprotein; ND, not determined.