Fig. 6: Functional improvement in perfused liver constructs.
From: Large-scale perfused tissues via synthetic 3D soft microfluidics
a Hematoxylin and eosin of a transverse section of liver tissue construct with hepaptocyte-like morphology and no visible indication of apoptosis. b Immunofluorescence images showing presence of Alpha Fetoprotein (AFP) and hepatic P450 cytochrome CYP3A4, c Alpha-1 antitrypsin (AAT) and Cytokeratin 19 (KRT19). d Multiple drug resistance-associated protein (MRP2) and α1-antitrypsin (AAT), e Basic hepatic markers albumin (ALB) and hepatic nuclear factor (HNF4α) expression (f) Vimentin (VIM) and albumin (ALB). Scale bar 70 µm. Representative images on (a) through (f) were acquired in three independent experiments; all experiments produced similar results. g Heatmap representation of fold change gene expression levels normalized to control 2D cell culture and compared to standard hepatic organoids and perfused liver constructs; rows are centered and scaled. Gene expression data for hepatic 2D culture and hepatic organoids are from Kumar et al.103. Color bar represents normalized fold change (dimensionless) in the expression of the corresponding genes. h Perfused hepatic constructs produced albumin (97.6 ± 23.1 ng/h/106 cells, n = 3) and urea (i) (1.4 ± 0.2 µg/h/106 cells, n = 3). j Quantification of drug metabolism in perfused hepatic constructs. Based on the data for Quinidine (left, n = 3) Metaclopramide (middle, n = 3) and Theophylline (right, n = 3), prediction of human in vivo drug clearance was done for the corresponding drugs based on well-stirred model, with calculated predicted fold error (PFE) shown. Data are derived from independent experiments and are represented as mean ± SEM.
