About the liver

The liver is the largest organ of the human body. It does many jobs, including removing toxins from the blood, helping to digest food and fighting infections. It is the only organ in the body that can regenerate itself after damage.

The cells that do the work in the liver are called hepatocytes. On average, each hepatocyte lives for around 200 to 300 days. In a healthy liver, hepatocytes can divide to make copies of themselves. This means they can replace the cells that die and can even repair some kinds of damage. If the liver is severely injured, another type of liver cell may come to the rescue: these cells are called oval cells. Oval cells are thought to be the liver’s resident stem cells and have the potential to make new hepatocytes. However, scientists are still investigating exactly what oval cells are, how they work and how we can make them produce hepatocytes more efficiently.

A piece of mouse liver containing hepatocytes and oval cells. Oval cells are thought to be the stem cells of the liver. They appear only to become active under certain circumstances, e.g. when hepatocytes cannot repair damage.

What goes wrong in chronic liver disease

In chronic liver disease (also called cirrhosis), a lot of liver damage happens over a long period of time. The normal repair processes are impaired and scars are formed in the liver. The only currently available treatment for patients with chronic liver disease is an organ transplant. Transplants are expensive and there are not enough organ donors to treat all the patients. Alternative therapies must therefore be found for patients with liver cirrhosis. 

Stem cell therapies for liver disease

In the long term, stem cells might provide new ways to treat chronic liver disease:

1. Researchers are working to identify liver stem cells more precisely, and to understand how they could be used to treat patients.
2. Embryonic stem cells or induced pluripotent stem cells might be used to make new hepatocytes in the laboratory for patients whose liver can no longer regenerate. However, there are still a number of fundamental questions that must be answered before this kind of treatment can be developed. For example, it will be important to find out which molecular cues are required by stem cells to make hepatocytes.

Using bone marrow cells to treat chronic liver disease

Another route to new treatments might be to use cells made from a patient’s own bone marrow to help repair damaged liver tissue. These cells are called macrophages. Under normal circumstances, macrophages cannot make new liver cells and scientists don’t yet understand exactly how they help the liver. However, macrophages have been tested in mice with damaged livers and early results look promising. In the laboratory:

• Bone marrow cells are harvested from the thigh bone of a mouse.
• The bone marrow contains a mixture of cells. The cells are grown under carefully controlled conditions to make many macrophages.
• The macrophages are put into the diseased liver of the mouse.
• The macrophages have a beneficial role in regenerating liver tissue and reversing scarring in the liver. When scarring is reduced, the liver is able to work better.

An important goal for research now is to understand what the macrophage cells do in the liver. This is an essential step before any treatment is developed for patients. Researchers are trying to answer this question and hope that the first clinical trials to test the safety of a macrophage-based treatment may begin in the next 5 years or so. There is a lot of work still to do, but if such a treatment can be developed, it will have an important advantage: The macrophage cells would be grown from the patient’s own bone marrow or blood so should not be rejected by the immune system, as sometimes happens with organ transplants.

Current research

Research is underway to gain a better understanding of the healthy liver and how new cell therapies could work. Scientists are also developing more effective ways to grow large numbers of liver cells (hepatocytes) from embryonic stem cells or induced pluripotent stem cells in the lab. Such research is not only useful for potential new therapies. In the shorter term, lab-grown hepatocytes are likely to play an important role in the development of new drugs and artificial liver machines.

Find out more

Liver good life - an animated film about the liver
The British liver trust - information for patients
The European Association for The Study of the Liver - information on EU policy
MRC Centre for Regenerative Medicine - lab studying bone marrow macrophages and the liver
MRC Centre for Regenerative Medicine - lab studying ways to make hepatocytes from embryonic stem cells

Acknowledgements and references

This factsheet was created by Caroline Pope and reviewed by David Hay, David Tosh and Clare Blackburn.
Cell images by Caroline Pope,  David Hay and Luke Bolter.