NC, Feb.13, 2018 – Scientists at Wake Forest Institute for Regenerative
Medicine (WFIRM) have
developed the most sophisticated mini-livers to date. These organoids can
potentially help scientists better understand certain congenital liver diseases
as well as speed up efforts to create liver tissue in the lab for
transplantation into patients.
model better mimics fetal development and function of the human liver,” said
Shay Soker, Ph.D., professor of regenerative medicine at WFIRM, which is part
Forest Baptist Medical Center.
“We expect these organoids to advance our understanding of how liver diseases –
especially congenital diseases -- start and progress so improved treatments can
was lead researcher on the study, which is reported in Hepatology.
creation of living mini-organs is a relatively new area of science with the
potential to replace animal models that are not always accurate. The liver
organoids, made with human cells, are less than one-third inch in diameter.
While scientists have already created liver organoids to screen new drugs for
liver toxicity, the livers developed in this research represent several
“firsts” in the quest to build a functional model of human liver development.
make the organoids, scientists allow fetal liver progenitor cells, an immature
cell that is destined to become a specialized liver cell, to self-assemble on a
small disc. The discs are made of ferret liver that has been processed to
remove all of the animal’s cells. The resulting organoids, which assemble
within two to three weeks, are the first to model actual human liver
research is significant in two ways. First, the scientists showed that these
organoids generated hepatocytes, the main functional cells of the liver. This
achievement represents a milestone in work to create truly functional
bioengineered liver tissue for transplantation into patients.
while other scientists have shown that lab-grown livers can generate bile
ducts, this is the first study to show the stepwise
maturation of bile ducts exactly as can be observed in the human fetal liver.
Bile ducts carry bile, a fluid that is secreted by the liver and
collected in the gall bladder to digest fats. This model of bile ductal
development can potentially be used to study the hereditary disease biliary
atresia that occurs in infants. With this disease, bile drainage is impaired,
making it fatal in the more severe cases.
“Altogether, the team
has created a laboratory model of human liver development and disease that will help advance our understanding about bile duct
formation,” said first co-author Pedro Baptista, Pharm.D., Ph.D., who was with
WFIRM at the time of the research.
“This is a big step toward advancing the bioengineering of
functional livers and bile ducts and we look
forward to using it in a variety of ways to mprove human health,” said first
co-author Dipen Vyas, Ph.D., also at WFIRM at the time of the research.
research was sponsored by the National Institutes of Health and the state of
authors were Dipen Vyas, Ph.D., Biorg Inc., and Pedro
Baptista, Pharm.D., Ph.D., Health Research Institute of Aragon, Spain; Matthew
Brovold, B.Sc., Brandon Gaston, B.Sc., Chris Booth, B.Sc., Michael Samuel,
B.Sc., and Anthony Atala, M.D., Wake Forest Baptist; and Emma Moran, Ph. D.,
Cook Research Inc.