In the quest to grow replacement human organs in the lab, livers are no doubt at the top of many a barfly’s wish list. With its wide range of functions that support almost every organ in the body and no way to compensate for the absence of liver function, the ability to grow a replacement is also the focus of many research efforts. Now, for the first time, researchers have been able to successfully engineer miniature livers in the lab using human liver cells.
The ultimate aim of the research carried out at the Institute for Regenerative Medicine at Wake Forest University Baptist Medical Center is to provide a solution to the shortage of donor livers available for patients who need transplants. Additionally, the laboratory-engineered livers could also be used to test the safety of new drugs.
The livers engineered by the researchers are about an inch in diameter and weigh about 0.2 ounces (5.7 g). Even though the average weight of an adult human liver is around 4.4 pounds (2 kg), to meet to minimum needs of the human body the scientists say an engineered liver would need to weigh about one pound (454 g) because research has shown that human livers functioning at 30 percent of capacity are able to sustain the human body.
“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 Shay Soker, Ph.D., professor of regenerative medicine and project director. “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.”
How the livers were engineeredTo engineer the organs, the scientists took animal livers and treated them with a mild detergent to remove all cells in a process called decellularization. This left only the collagen “skeleton” or support structure which allowed the scientists to replace the original cells with two types of human cells: immature liver cells known as progenitors, and endothelial cells that line blood vessels.
Because the network of vessels remains intact after the decellularization process the researchers were able to introduce the cells into the liver skeleton through a large vessel that feeds a system of smaller vessels in the liver. The liver was then placed in a bioreactor, special equipment that provides a constant flow of nutrients and oxygen throughout the organ.
After a week in the bioreactor system, the scientists observed widespread cell growth inside the bioengineered organ and documented the progressive formation of human liver tissue, as well as liver-associated function.
Although the ability to engineer a liver with animal cells had been demonstrated previously, this is the first time human liver cells had been used to successfully generate a functioning human liver.
Pedro Baptista, PharmD, Ph.D., lead author on the study, said “our hope is that once these organs are transplanted, they will maintain and gain function as they continue to develop,” he said. He added that bioengineered livers could also be useful for evaluating 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," he said.
The researchers said the current study suggests a new approach to whole-organ bioengineering that might prove to be critical not only for treating liver disease, but for growing organs such as the kidney and pancreas. Scientists at the Wake Forest Institute for Regenerative Medicine are working on these projects, as well as many other tissues and organs, and also working to develop cell therapies to restore organ function.
The team’s research was presented Sunday at the annual meeting of the American Association for the Study of Liver Diseases in Boston and will be published in an upcoming issue of the journal Hepatology.