Could solve problem of lack of liver donors for those who need transplants

Wake Forest University Baptist Medical Center researchers at the Institute for Regenerative Medicine are the first to successfully use human liver cells to create miniature, functional livers in a laboratory setting.

Pedro Baptista, PharmD, Ph.D., lead author of the study, and Shay Soker, Ph.D., project director and professor of regenerative medicine, have become the first researchers to engineer miniature livers that are capable of functioning like the human liver. This study aims to solve the shortage of donor livers available for those who need transplants. 

"We are excited about the possibilities this research represents, but must stress that we're at an early stage and many technical hurdles must be overcome before it could benefit patients," said Soker. "Not only must we learn how to grow billions of liver cells at one time in order to engineer livers large enough for patients, but we must determine whether these organs are safe to use in patients."

To ensure the safety of these miniature livers, researchers are looking to test them on animal models first. This seems like a simple test because these miniature livers, in fact, are animal livers to begin with. But these animal livers went through a process called decellularization, which means a mild detergent was used to remove all cells in the liver, leaving only the support structure. Then, two types of human cells replaced the original animal cells in the liver. These human cells are progenitors, which are immature liver cells, and endothelial cells, which line the blood vessels. 

Researchers then placed the liver into a bioreactor, which provides a continuous flow of oxygen and nutrients throughout the organ. The bioengineered liver was observed during its time in the bioreactor system, and after one week, widespread cell growth, the formation of human liver tissue and liver-associated function occurred within the organ. These were significant findings because up until this point, researchers had already demonstrated the ability to create a liver with animal cells, but they hadn't yet demonstrated the ability to engineer functional livers with human cells.

The next step is to see if these miniature livers can continue to function normally after being transplanted into an animal model. 

The researchers would like to see this new development lead to the production of whole-organ bioengineering, which could treat liver disease and result in the growing of other organs such as the kidneys and pancreas. In addition, bioengineered livers could be used to help evaluate the safety of new drugs. 

"This would more closely mimic drug metabolism in the human liver, something that can be difficult to reproduce in animal models," said Baptista. 

The abstract, "The Use of Whole Organ Decellularization for the Bioengineering of a Human Vascularized Liver," was presented Sunday at the annual meeting of the American Association for the Study of Liver Diseases in Boston.

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