Scientists have managed to successfully engineer small functioning livers from human liver cells in a laboratory setting. They say this is the first step towards creating functioning livers for transplantation. They now plan to determine whether the livers will function properly when transplanted into an animal model. This research was presented by scientists from the Institute for Regenerative Medicine at Wake Forest University Baptist Medical Center at the American Association for the Study of Liver Disease meeting in Boston, and will also be published in the medical journal Hepatology.
Currently, the scientists explain, the demand for donor livers far outstrips supply. This new technology could eventually solve a serious shortage problem.
New medications can also be tested on lab-engineered livers.
Project director, Shay Soker, Ph.D., a professor of regenerative medicine, said:
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. 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.
Never before have human liver cells been used to create livers in the laboratory, lead author Pedro Baptista, PharmD, Ph.D. explained.
Baptista said:
Our hope is that once these organs are transplanted, they will maintain and gain function as they continue to develop.
For a liver to meet the basic requirements of a human being, it needs to weight about 1 pound, which is still smaller than the average human liver. These laboratory-engineered ones weigh approximately one-fifth of an ounce. Experts say that a liver that functions at just 30% of capacity can keep a person alive.
The researchers used a process called decellularization to remove all the cells from animal livers – a mild detergent was utilized for this. When the cells are removed a support structure – a collagen skeleton – is left. The original animal liver cells were replaced with progenitors (immature human liver cells) and endothelial cells (those that line blood vessels).
A large vessel that feeds a system of smaller vessels in the liver, which remains intact after the decellularization process, was used to get the cells into the liver skeleton. They then placed the liver into a special device that feeds it essential oxygen and nutrients, called a bioreactor.
Over the following week they documented the gradual development of human liver tissue, as well as liver-type functions. Cell growth was “widespread” inside the bioengineered liver.
Although livers with animal cells have been engineered before, nobody knew whether making a functional human liver was possible.
The scientists believe the findings of their study may have an important impact on future treatment of liver, kidney, pancreas and other organ diseases, by growing them in the lab.
Current research at Wake Forest is looking into growing other organs and tissues, as well as the restoration of organ function through cell therapies.
Livers bioengineered in the lab could also be used when evaluating the safety of a new medication, the researchers explain. Results would be more accurate and relevant than current animal model studies.
Baptista said:
This would more closely mimic drug metabolism in the human liver, something that can be difficult to reproduce in animal models.
Written by Christian Nordqvist