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2017 ; 242
(16
): 1593-1604
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Opportunities and challenges in the wider adoption of liver and interconnected
microphysiological systems
#MMPMID28504617
Hughes DJ
; Kostrzewski T
; Sceats EL
Exp Biol Med (Maywood)
2017[Oct]; 242
(16
): 1593-1604
PMID28504617
show ga
Liver disease represents a growing global health burden. The development of
in vitro liver models which allow the study of disease and the prediction of
metabolism and drug-induced liver injury in humans remains a challenge. The
maintenance of functional primary hepatocytes cultures, the parenchymal cell of
the liver, has historically been difficult with dedifferentiation and the
consequent loss of hepatic function limiting utility. The desire for longer term
functional liver cultures sparked the development of numerous systems, including
collagen sandwiches, spheroids, micropatterned co-cultures and liver
microphysiological systems. This review will focus on liver microphysiological
systems, often referred to as liver-on-a-chip, and broaden to include platforms
with interconnected microphysiological systems or multi-organ-chips. The
interconnection of microphysiological systems presents the opportunity to explore
system level effects, investigate organ cross talk, and address questions which
were previously the preserve of animal experimentation. As a field,
microphysiological systems have reached a level of maturity suitable for
commercialization and consequent evaluation by a wider community of users, in
academia and the pharmaceutical industry. Here scientific, operational, and
organizational considerations relevant to the wider adoption of
microphysiological systems will be discussed. Applications in which
microphysiological systems might offer unique scientific insights or enable
studies currently feasible only with animal models are described, and challenges
which might be addressed to enable wider adoption of the technologies are
highlighted. A path forward which envisions the development of microphysiological
systems in partnerships between academia, vendors and industry, is proposed.
Impact statement Microphysiological systems are in vitro models of human tissues
and organs. These systems have advanced rapidly in recent years and are now being
commercialized. To achieve wide adoption in the biological and pharmaceutical
research communities, microphysiological systems must provide unique insights
which translate to humans. This will be achieved by identifying key applications
and making microphysiological systems intuitive to use.
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