The liver is one of a kind. With regeneration properties only thought to be possible in movies, it has the ability to regenerate itself after catastrophic damage. It has been estimated that it can regrow to a normal size after an astonishing 90% of it has been removed. As phenomenal as the liver is, it cannot be seen as invincible. There are numerous diseases which can damage the liver past the point of repair. Some of these diseases include cancer, fatty liver disease, medication overdoses and hepatitis. Whilst researchers know that the liver can regenerate itself, the exact type of cells responsible and their location are highly debated. It has been suggested that stem cells are the ones responsible for producing new liver cells, but other liver cells called hepatocytes have also been implemented. If the renewal process fails, then a transplant is required.

The liver is the largest organ in the human abdomen, weighing around 1.4kg, and is divided into sections called lobes. The liver has a range of functions which include the production of certain molecules and the destruction of others. It is most famously known for the disposal of toxic substances – including alcohol. It does this through the production of bile, which acts to break down substances and digest them to fats. Fat droplets are collected in ‘bubbles’, so that they can be transported through the watery environment of the body. Bile is moved through small vessels in hepatocytes to the gallbladder, and then onto the intestine. After this cycle, the bile is returned to the liver. The liver has additional role in the immune system.

So, what is liver regeneration?

Liver regeneration is the process by which the liver replaces lost tissue. In its normal form, the liver is quiescent, which means that under a microscope, only one cell among thousands will be seen dividing. But, when the liver is damaged (either by a wound or a chemical), the cells are stimulated to divide and grow. In tissues such as the intestines and skin, the maintenance of cells is done by stem cells and a high turnover. This contrasts the liver, where the turnover is low. For example, if 50-60% of liver cells are destroyed due to a drug overdose, the liver can totally repair itself in 30 days, providing there aren’t any further complications. This ability to regenerate is an amazing evolutionary adaptation, as the liver is expected to be injured by toxins whilst detoxifying the body.

What are the phases of liver regeneration?

Liver regeneration beings with the priming phase. In this phase, the hepatocytes (cells of the liver) are prepared to respond to growth factors, and more than 100 genes are activated. The liver cells are primed to re-enter the first stage of the cell cycle. The cell cycle is the process in which cells divide to create new cells. After the priming phase, growth factor receptors are activated, in the proliferation phase, with factors necessary for liver regeneration being stimulated. The final step in regeneration is the cessation of proliferation (cell growth). This occurs when the liver’s normal mass has been restored. The mechanisms responsible for this are not currently well know.

Liver regeneration and regenerative medicine

For most end-stage liver diseases, transplantation is the primary option. Despite this being the main option, donor organs are hard to come by, meaning some patients die of liver failure before a suitable donor can be found for them. Another consideration in transplantation is whether the patient is healthy enough to survive the surgery and able to comply with medication regimes and medical advice. It has been found that adherence to medication regimes is correlated to the success of a liver transplant. Aging populations with modern lifestyles increase the number of people suffering from liver disease. This has fuelled the need for research into regenerative treatment options.

An area called liver regenerative medicine is a field focused on the creation of new therapies using stem cells, gene therapy and engineered tissues to repair the affected organ. One such stem cell being investigated for regenerative medicine is the mesenchymal stem cell. These stem cells can be extracted from bone marrow, umbilical cord blood and adipose tissue. They can be expanded in great numbers rapidly. This type of stem cell can be transformed into a liver cell, where it can promote liver regeneration and prevent scarring of the liver. There are less ethical issues concerning mesenchymal stem cells than embryonic stem cells, as they are not derived from embryos.