The liver has the greatest regenerative capacity of any organ in the body. However, when the liver is injured beyond its ability to regenerate itself, and a transplant is not readily available, there are few options for patients.
Led by Scott Nyberg, M.D., Ph.D., researchers are refining their own version of a bioartificial liver, known as the Spheroid Reservoir Bioartificial Liver (SRBAL). This device contains pig liver cell (hepatocyte) spheroids, which replace a patient's liver function.
“Ideally, the artificial liver would bridge the gap until a donor liver becomes available or if it could help the patient avoid the need for a transplant altogether,” says Dr. Nyberg.
While the artificial liver device has been successfully demonstrated on pigs with acute liver failure, the ultimate goal is the bedside treatment of patients in liver failure. With a research grant from Regenerative Medicine Minnesota, Dr. Nyberg and his team are continuing to study whether the artificial liver could function similar to a kidney dialysis machine. The patient would be connected to the device, and much like dialysis, the artificial organ would, perform critical bodily functions while the liver heals and regenerates.
“The results of our third large animal study were published in January 2019,” says Dr. Nyberg. “Pigs were chosen for the early studies because their metabolism is similar to ours and because they could provide an abundant supply of liver cells.”
In the treatment group, all of the animals survived the therapy and were up walking around with recovered livers at the end of the study. The results have paved the way for future clinical trials.
Although the SRBAL is similar to kidney dialysis, the liver is more complicated. It does metabolic activities, detoxifies wastes, and synthesizes proteins. Because of this, the SRBAL incorporates living cells– in this case, from pig livers - to carry out such vital functions for a patient.
“We’re ready for to move into Phase I trials in humans,” says Dr. Nyberg. “However, funding a medical device trial using living cells in humans is quite expensive, and we’ll need to build a new clinically acceptable SRBAL suitable for human use.”
Once funding is established and the new device developed, the first study in humans would be a Phase I safety study to make sure the machine is safe for use on people. Second is a dosing study to determine the efficient dose of liver cells to put in the bioreactor to repair the liver. Once the Phase I and Phase II studies are complete and encouraging, a Phase III, multicenter randomized study would follow.
“This is an exciting time for transplant surgery,” says Charles Rosen, M.D., director of the William J. von Liebig Center for Transplantation and Clinic Regeneration at Mayo Clinic. “The need for organ donation is high, and this research couldn’t come at a better time.”
SRBAL would be most appropriate for patients who have acute liver failure and are awaiting transplant, experience an overdose of medication, or those who aren’t candidates for liver transplant.
“There’s a lot of work to be done, but this is a promising solution to the donor organ shortage in some cases” says Dr. Nyberg. “Many acute liver failure patients would have the opportunity to recover, if only they had time for their liver to regenerate and heal.”