Scientists at Wake Forest Institute for Regenerative Medicine (WFIRM) have created an in vitro model of human liver development and disease, physiology, and metabolism that they believe will facilitate a better understanding of the mechanisms involved in hepatic and biliary development as well as aid in disease modeling and drug screening.
"This model better mimics fetal development and function of the human liver," said Shay Soker, Ph.D., professor of regenerative medicine at WFIRM. "We expect these organoids to advance our understanding of how liver diseases—especially congenital diseases—start and progress so improved treatments can be developed." Details on the research were published recently in Hepatology.
The liver organoids, which were 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 are unique in the contribution to the quest to build a functional model of human liver development, according to the team.
To make the organoids, the team allowed fetal liver progenitor cells to self-assemble on a small disc. The discs were made of ferret liver that has been processed to remove all of the animal's cells. The resulting organoids were assembled within two to three weeks.
The research is significant in two ways. First, the scientists showed that these organoids generated hepatocytes. This achievement will allow the creation of truly functional bioengineered liver tissue for transplantation into patients, they say. Second, while other scientists have shown that lab-grown livers can generate bile ducts, this is reportedly the first study to show the stepwise maturation of bile ducts exactly as can be observed in the human fetal liver. This model of bile ductal development can potentially be used to study the hereditary disease biliary atresia that occurs in infants.