Fig. 6

Engraftment and repopulation of uPA-NOG mouse liver with human HpSCs. a Macrophotography of a humanized liver 1 month after being transplanted with human HpSCs. b Human HpSC-derived liver structure in a humanized liver lobe (H&E). m mouse liver region, h human HpSC-derived liver region. Scale bar: 50 μm. c, d Immunohistochemistry used to distinguish human liver cells from mouse liver cells with anti-human ALB (red) and anti-human nuclear antigen (green). Nuclei stained with DAPI (blue). Scale bars: 50 μm (c) and 1000 μm (d). e Immunostaining of humanized liver with human ALB (red) and human CK19 (green). Nuclei stained with DAPI (blue). Scale bar: 50 μm. Results representative of at least three independent experiments. f Chimeric rate in uPA-NOG mice 1 month after donor cell transplantation. Data represent mean ± SEM (n = 8 independent experiments). Mann–Whitney test, **P = 0.0042 between human primary FLCs and human HpSCs. g Human albumin detection in mouse sera 1 month after donor cell transplantation. Data shown as mean ± SD (n = 5 independent experiments). Mann–Whitney test, P = 0.0079 between human primary FLCs and human HpSCs. ND undetectable. h Kaplan–Meier survival curve of uPA-NOG mice after human primary FLC and HpSC transplantation (n = 7 in each group). Log-rank (Mantel–Cox) test, P = 0.0001. i Pharmacokinetic analysis of serum metabolite 4-OH debrisoquine formation to debrisoquine in sera of human HpSC-derived humanized mice and sham mice. Data shown as mean value ± SEM (n = 3 independent experiments). Mann–Whitney test, P = 0.0159. See also Additional file 5: Figure S5. H&E hematoxylin and eosin, hALB human albumin, HpSC hepatic stem cell, FLC primary fetal liver cell, Tx treatment, CK cytokeratin, 4-OH-DB/DB 4-hydroxy-debrisoquine to debrisoquine