Miniature Human Livers Created in the Lab

Researchers have reached a significant first milestone in the pursuit to grow replacement livers in the lab. They are the first to use human liver cells to engineer effectively miniature livers that function--at least in a laboratory environment--similar to human livers. The next step is to see if the livers will continue to function after transplantation in an animal model.

The ultimate aim of the research, which was presented October 31, 2010, at the annual meeting of the American Association for the Study of Liver Diseases in Boston, MA, USA, is to provide a solution to the shortage of donor livers available for patients who need transplants. Laboratory-engineered livers could also be used to evaluate the safety of new drugs.

"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 at the Institute for Regenerative Medicine at Wake Forest University Baptist Medical Center (Winston-Salem, NC, USA). "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 engineer the organs, the scientists used animal livers that were treated with a mild detergent to remove all cells (a process called decellularization), leaving only the collagen "skeleton,” or support structure. They then replaced the original cells with two types of human cells: immature liver cells known as progenitors, and endothelial cells that line blood vessels.

The cells were introduced into the liver skeleton through a large vessel that feeds a system of smaller vessels in the liver. This network of vessels remains intact after the decellularization process. The liver was next positioned in a bioreactor, a dedicated device that provides a constant flow of nutrients and oxygen throughout the organ. After one week in the bioreactor system, the scientists documented the progressive formation of human liver tissue, as well as liver-associated function. They observed extensive cell growth inside the bioengineered organ.

Bioengineered livers could also be beneficial for evaluating the safety of new drugs, as these would more closely mimic drug metabolism in the human liver, something that might be difficult to reproduce in animal models.

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Institute for Regenerative Medicine at Wake Forest University Baptist Medical Center