Fig. 3. Human liver tissue seed graft function.

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Fig. 3. Human liver tissue seed graft function. Human liver tissue seed graft function. Mice were implanted with liver seed grafts, and the host mice were treated intermittently with NTBC to induce liver injury and repair (14 days off, followed by 3 to 4 days on; gray bars). (A) Blood samples were collected weekly by retro-orbital bleeding. The concentration of human albumin in mouse serum was greater in animals with liver injury compared to controls [P < 0.0001, one-way analysis of variance (ANOVA)]. (B) Human albumin concentration for each animal averaged across all time points. (C) The concentrations of human transferrin, α1-antitrypsin, and fibronectin in mouse serum were greater in animals receiving intermittent NTBC treatment (liver injury) compared to controls at 80 days after implantation into FNRG mice. (D) mRNA expression analysis of explanted liver seed grafts demonstrated that 47 of 50 liver-specific genes were expressed in explanted liver seed grafts (denoted “Seed graft”) compared to 18 of 50 human genes expressed in HUVEC and NHDF cell lines. (E and F) Genes from each of the major hepatic drug metabolism pathways were expressed in liver seed grafts at levels similar to those of the human liver. (G and H) Mice with liver seed grafts were injected with rifampin solution (25 mg/kg, intraperitoneally) or vehicle control daily for 3 days and, again, 1 hour before sacrifice. (I) Rifampin induced greater CYP3A4 expression in expanded liver seed grafts compared to mice injected with vehicle control. *P < 0.05, ***P < 0.001 (Student’s t test). Kelly R. Stevens et al., Sci Transl Med 2017;9:eaah5505 Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works