UT Southwestern Medical Center Study Explains How Liver Cells Regenerate

The liver cells are one of the few cells in the adult human that can still re-enter the cell cycle and undergo regeneration after a significant level of damage. However, the liver can still lose this ability when exposed to severe stressors like Hepatitis, Cancers, Some drug overdoses, extreme trauma, or compromising of the vascular supply. These stressed conditions still account for the majority of the over 7000 liver transplants been carried out in the US alone.



Zones of the liver

Each of the liver lobules is made of liver cells arranged in 3 major zones.

  • Zone 1: This is the zone closest to the arteries that supply blood to the liver.
  • Zone 2: This is the area in-between the 2 other zones. It lies in the area between the blood supply and drainage and is the least affected in any case of toxic exposure of the liver. The function of hepatocytes in this zone is still less clear unlike the cells of zone 1 and zone 2 which are known to be highly metabolic in enzyme production and detoxification.
  • Zone 3: This is the zone closest to the venous drainage of blood from the liver.

Read Also: Liver Health: A List of the Best and Worst Foods for the Liver

Researches into the zone responsible for most of the liver generation process

A lot of controversies have beclouded the exact cells involved in this special ability of liver cells to regenerate, whether it is the hepatocytes themselves or the stem cells. Due to the uniqueness of this rare process, and its propensity to be replicated for other favorable uses, many scientific works in the past have been done to delineate this mechanism.

Recently, a Dr. Hao Zhu led team from the Children’s Medical Center Research Institute at UT Southwestern Medical Center carried out a study which was funded partly by the National Institute of Environmental Health Sciences (NIEHS), NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and National Cancer Institute (NCI) and was published on 26th February 2021.

The team used a total of 14 different lines of mice out of which they crated 11 for the new study. Each of the mouse lines was programmed to express a different group of liver cells via a fluorescent marker. With this, the cells could now be monitored pre and post-liver damage to different parts of the liver.

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In the end, it was discovered that it was hepatocytes, mostly of zone 2 origins, and not stem cells that are responsible for the replication and regeneration. These Zone 2 hepatocytes also created new cells to replace zone 1 and zone 3 hepatocytes which are damaged during liver toxicity. A specific pathway that drives zone 2 cells to the sites of damages was also discovered and was sensitive to interruption of the pathway.

In the same vein, another team from Shanghai, at the Institute of Biochemistry and Cell Biology researched the same topic using a different approach and arrived at a similar conclusion by tracking the origins of new hepatocytes.


Although more experiments will be needed to have a clearer understanding of liver cell regeneration, it appears that the zone 2 cells which are least affected by liver toxicities play a higher role in the regeneration of cells of other zones. A full understanding of this will shape our future in overall cell regeneration techniques.

Read Also: Liver Disease: Stool Based Test Can Diagnose Cirrhosis With a 90% Accuracy


Liver homeostasis is maintained by midlobular zone 2 hepatocytes

Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair



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