Time to recover - technology hope for liver disease

For people with severe liver disease, time can be the enemy. As the liver loses its ability to remove toxins and maintain the body’s chemical balance, the kidneys and brain can also begin to fail. A transplant may offer the only realistic lifeline, but donor organs are scarce and many patients become too ill while waiting.

The team are developing a different approach using small pieces of living human liver tissue grown from stem cells. Their goal is not to create an entire replacement liver, but to develop a simple implant that could support a failing organ when the patient has little time to spare.

The proposed implant would sit beneath the skin, where it could connect to the bloodstream and perform some of the biochemical work the damaged liver can no longer manage. By temporarily reducing the burden on the liver, the researchers hope to give it more time—and potentially an opportunity to recover.

This is particularly challenging because the liver does far more than filter waste. It produces essential proteins, processes medicines and nutrients, and transforms toxins into substances the body can eliminate. Machines can replace some kidney functions, but reproducing the liver’s complex biological work is much more difficult.

Hay’s team begins with stem cells — cells that can be guided to develop into specialised cell types. Some are directed towards becoming liver cells, while others become endothelial cells, which form the lining of blood vessels.

The cells are brought together in tiny spheres measuring approximately 0.4 millimeters' across. Within these structures, the endothelial cells begin to form an early vascular network. This is essential because living tissue needs a reliable supply of oxygen and nutrients if it is to survive and function after transplantation.

Over six weeks in the laboratory, the tissue became more liver-like. It produced increasing amounts of albumin, an important protein normally made by the liver, maintained production of alpha-1-antitrypsin and continued to metabolise substances. In other words, the cells did not simply resemble liver tissue—they began to behave like it.

A crucial test was whether the tissue would continue working outside the laboratory in which it had been developed. The material was packaged, transported to an independent laboratory and transplanted into mice by a third-party team.

Human albumin was subsequently detected in the animals’ blood. Tissue placed beneath the kidney capsule continued producing a measurable signal for at least two weeks. Tissue implanted beneath the skin produced its strongest signal during the first few days, although this had returned to baseline after two weeks.

The results demonstrate both the promise of the approach and its greatest current limitation. The tissue can survive transportation, transplantation and connection with a living body - but it must function for much longer before it could provide meaningful support for patients.

The team’s long-term aim is to create a small implant that could be placed beneath the skin using a relatively simple procedure under local anaesthetic. Once implanted, it would attract blood vessels, connect to the circulation and help process some of the substances that accumulate when the liver begins to fail.

This would not be a new liver growing beneath the skin. It would be living tissue providing help from the sidelines - potentially keeping liver function stable long enough for the patient’s own organ to recover or for another treatment to become available.

Turning this laboratory advance into a clinical treatment will require extensive further work. The researchers must demonstrate that the tissue can be manufactured consistently, remains stable, is safe and interacts appropriately with the immune system. Its performance must also be tested in models of liver disease, not only in otherwise healthy animals.

If the implant can be shown to be safe, durable and effective, it could offer critically ill patients something exceptionally valuable: support for a failing liver, protection for other organs—and more time for recovery.

In his role as Director of Translation at the Zhejiang University-University of Edinburgh Institute (ZJE) Professor Hay has established Stimuliver to take the technology forward.