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Cardio- and hepatotoxicity are the primary causes for late-stage failures and post-market withdrawals
100 m
100 m
H&E (20x)
E-Cadherin (20x)
Single- or Multi-unit bioprinted liver tissues were constructed from hepatocytes or hepatocyte-like cells and non-parenchymal cells, and were characterized by a tissuelike cellular density and tight intercellular junctions.
These liver tissues remained stable for 135 hours and retained key liver functions, including inducible CYP1A2 and CYP3A4 activity.
Constructed w/ 1 hepatocytes, hepatic stellate cells, and endothelial cells
135Hrs
Constructed with HepaRG cells, hepatic stellate cells, and endothelial cells
Bioprinted liver tissues possess the ability to synthesize cholesterol, a hallmark liver-associated function. Cholesterol biosynthesis is retained and even increases over time in culture.
100 m
Bioprinted human liver tissues are characterized by cell-specific compartments that enable reproduction of native tissue-like architectural patterns and the establishment of controlled cell-cell interfaces.
Copyright 2013 Organovo Holdings, Inc.
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100 m
H&E / 20x
100 m
CD31 / 20x
Bioprinted liver constructs, generated from iPSC-derived hepatocyte-like cells (iCells; Cellular Dynamics, Inc.), are well organized, develop microvascular networks over time, and produce significantly more albumin per cell than matched 2D controls.
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Conclusions
Bioprinting enabled highly reproducible fabrication of architecturally and compositionally defined 3D tissues into standard tissue culture formats Bioprinted 3D liver tissues exhibited several key unique features that remained stable over time
Tissue-like cellular density with high viability and well-organized microarchitecture (microvasculature, tight junctions) H&E / 20x Cell type-specific compartmentalization , with establishment and retention of userdefined spatial localization of parenchymal and non-parenchymal cells Multi-layered architecture ranging from 250-500 microns in thickness
3D liver tissues possessed critical liver functions, including albumin production, cholesterol biosynthesis, fibrinogen and transferrin production, and inducible CYP1A2 and CYP3A4 activities Per-cell production of Albumin by 3D bioprinted tissues was 5-9x greater than matched 2D controls, suggesting superior functional performance in 3D
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