The liver is the largest internal organ in our body. It plays a vital role in food metabolism, energy storage, and toxin elimination. Almost 2 million people die every year due to liver disorders and no proper treatment, representing a significant global health challenge. Also, liver failure is the end stage of many lethal diseases like alcoholic hepatitis, liver cancer, and Hepatitis B infection. In such situations, liver failure results from the death of hepatocytes, a major cell type of liver.

Organ transplant is the only available therapeutic option for people with last-stage liver disorders. However, it is difficult to find donors that match the immune system. Therefore, only 10% of patients requiring a transplant receive a new working liver, and many patients die before they find a suitable liver.

Researchers are finding the potential of stem cell research to provide treatment to patients who do not have access to liver transplants.

Pluripotent stem cells can differentiate into any type of cell in the body. These stem cells can be produced in large numbers in the lab. They can be differentiated into working cells with the goal that they will be able to combine into a human organ. To carry out physiological activities successfully or even replace the need to donate organs for transplant.

For more than 20 years, scientists have been working on the production of functional liver cells. Scientists, after great efforts, found ways to copy various stages of embryonic liver development. Stem cell-derived hepatocytes produced are comparable to normal liver cells, in terms of food metabolism, energy storage, and elimination of toxins.

However, scientists are still working to see whether these stem cell-derived liver cells are safe for patients. They are also studying if the artificial liver, created by these cells, would function outside of the body.

Research on stem cell-derived liver cells

Recently, a group led by Mureo Kasahara at the National Center for Child Health and Development in Japan treated a six-day-old baby with pluripotent stem cell-derived hepatocytes for the first time. The baby suffered from a rare genetic urea cycle disorder. This resulted in the buildup of ammonia in the baby’s blood due to the liver’s inability to break down ammonia. The usual treatment for this disease is liver transplantation but due to the complexity, it is too dangerous until 3-6 months.

To pass the time until the baby could safely receive the transplant, doctors decided to try a novel stem cell treatment with the hope to provide temporary support. Doctors injected stem cell-derived hepatocytes into the baby’s liver. Notably, after the treatment, the level of ammonia in the blood stabilized, giving the baby five months to survive.

Later, the baby received a successful liver transplant from the father and is now healthy. Further study to test the safety and efficiency of this procedure is still in the process however, it proved to be a promising finding. This gave the baby some time until transplantation was possible.

Further research to treat liver disorders

Furthermore, researchers are finding ways that stem cell-derived liver cells might help patients through external devices. The dialysis-like device created from these cells can be used as an alternative to transplantation. It will treat liver cirrhosis by clearing blood toxins.

Such a machine, also known as a bioartificial liver, may ease the symptoms of liver failure. It will also extend the time until a liver transplant is needed. “We are currently using these stem cell-derived hepatocytes to devise a bioartificial liver system to treat liver failure patients,” said Dr. Xiaolei Shi, chief surgeon at the Drum Tower Hospital of Nanjing University, China.

Shi and colleagues used stem cell-derived hepatocytes to make “mini liver tissues,” called hepatic spheroids. In preclinical studies, they created bioartificial liver using spheroids that rescued pigs from severe liver failure. These results are important because pigs are similar in size and weight to humans. Hence, this helps to understand how these machines may function in human patients. This research is important for moving ahead with clinical trials in humans.

Summary

Although there has been significant progress but there are also certain challenges. There are concerns about whether stem cell therapy may form tumors after transplant.

External devices, however, physically separate stem cell derivatives from patients, which could overcome certain safety issues as cells can be removed if any problem arises.

The latest advances shed light on ways that stem cell-derived liver cells may be used to help patients with various liver diseases. Current research will continue to explore how pluripotent cell therapies can be used safely to help treat many patients worldwide.