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2017 ; 10
(ä): 186-191
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Scaffold-free 3D bio-printed human liver tissue stably maintains metabolic
functions useful for drug discovery
#MMPMID28955746
Kizawa H
; Nagao E
; Shimamura M
; Zhang G
; Torii H
Biochem Biophys Rep
2017[Jul]; 10
(ä): 186-191
PMID28955746
show ga
The liver plays a central role in metabolism. Although many studies have
described in vitro liver models for drug discovery, to date, no model has been
described that can stably maintain liver function. Here, we used a unique,
scaffold-free 3D bio-printing technology to construct a small portion of liver
tissue that could stably maintain drug, glucose, and lipid metabolism, in
addition to bile acid secretion. This bio-printed normal human liver tissue
maintained expression of several kinds of hepatic drug transporters and metabolic
enzymes that functioned for several weeks. The bio-printed liver tissue displayed
glucose production via cAMP/protein kinase A signaling, which could be suppressed
with insulin. Bile acid secretion was also observed from the printed liver
tissue, and it accumulated in the culture medium over time. We observed both bile
duct and sinusoid-like structures in the bio-printed liver tissue, which
suggested that bile acid secretion occurred via a sinusoid-hepatocyte-bile duct
route. These results demonstrated that our bio-printed liver tissue was unique,
because it exerted diverse liver metabolic functions for several weeks. In
future, we expect our bio-printed liver tissue to be applied to developing new
models that can be used to improve preclinical predictions of long-term toxicity
in humans, generate novel targets for metabolic liver disease, and evaluate
biliary excretion in drug development.