Mature liver cells trigger regeneration in response to neighboring injury

Acetaminophen is the most frequently taken fever and pain medication worldwide, but overdosing can be toxic to liver cells. In the United States, about 1,600 cases of acute liver failure and 500 deaths occur each year due to acetaminophen overuse and liver failure. Although the liver has a remarkable potential to regenerate and recover from injury, scientists are seeking to better understand how this happens after acetaminophen toxicity.

Liver regeneration has been studied for decades, primarily through removing sections of the organ, yet there is still controversy among researchers regarding the source of new liver cells, and whether they originate from stem cells in the liver or from pre-existing mature liver cells which start multiplying after injury. A deeper understanding of mechanisms at play is essential to come up with strategies to boost liver regeneration in patients.

Towards this goal, Tomomi Aoyagi and colleagues from Kyushu University, Japan, studied the behavior of single cells in the mouse liver after acetaminophen injury and noticed that regeneration likely originated from a specific type of cell. The work was recently published in Stem Cell Reports. In their experiments, mature liver cells which were in direct contact with injured or dying cells transitioned to a more immature state and started to divide rapidly. Direct contact to damaged tissue was crucial for this transition, suggesting that signals from dead or dying cells instructs neighboring cells to start a regenerative program. Importantly, the researchers found a similar population of immature, dividing liver cells adjacent to injured tissue in biopsies from patients with drug-induced liver injury, suggesting that liver regeneration in humans follows similar principles.

Understanding how injured tissues instructs the neighboring cells to start a repair program may lead to more effective treatments for drug-induced liver injury and insights into strategies to treat liver failure, which can only be cured by transplantation.