Tissue architecture affects function of expanded liver seed grafts

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Fig. 2. Human liver tissue seed grafts expand after host liver injury.

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Fig. 6. Tissue architecture affects function of expanded liver seed grafts. Tissue architecture affects function of expanded liver seed grafts. (A) Human liver tissue seed grafts were created in three different constructs: (left) human hepatocytes, HUVECs, and NHDFs randomly organized as single cells within a fibrin hydrogel; (middle) human hepatocytes, HUVECs, and NHDFs in tri-cell aggregates randomly seeded in a fibrin hydrogel; and (right) human hepatocytes and NHDFs in aggregates, and HUVECs in endothelial cords, then combined in a fibrin hydrogel. (B) All three architectural conformations produced cytokeratin-18 –positive hepatic grafts after expansion in response to liver injury. Scale bars, 100 μm. (C) Graft size, as measured by histomorphometry, was not different between the three constructs. Hepatic function, as measured by human albumin and transferrin production, was increased in the original liver seed grafts. (D) Inclusion of both NHDFs and HUVECs in the liver seed grafts was necessary for maximal hepatic function after expansion in response to liver injury. (E) A comparison of the gene expression patterns in endothelial cell constructs with either random HUVECs or endothelial cell cords, 1 day after formation of the tissues in vitro, revealed that preorganization of HUVECs into endothelial cell cords resulted in increased expression of several key endothelial genes. *P < 0.05, one-way ANOVA. 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