Where does the liver get new cells from

Kirill Stasevich, "Science and Life" 

Our cells are not eternal: they wear out and die, although this happens in different organs and tissues at different rates. In order to compensate for cellular losses, there are stocks of stem cells that retain the ability to divide. Such stocks of not fully specialized, capable of dividing progenitor cells exist in most organs. For example, if you take blood, then its red blood cells live for 100-120 days, after which they are absorbed by immune "cleaners", and new red blood cells formed in the bone marrow come to replace them. After division, the progenitor stem cell may remain as unspecialized as it was, or it may complete differentiation and become a "specialist" capable of doing a particular job well, but no longer able to reproduce. 

As we have said, cellular regenerative reserves exist in most organs (although, unfortunately, such cells are inactive in our heart). It is obvious that renewal processes should be especially active where biochemical work is in full swing, where new vitamins are synthesized, toxins are neutralized, where metabolic switches are important for the whole organism – that is, in the liver. 

Indeed, liver cells, hepatocytes, are regularly updated, but for a long time no one knew how this happens – stem cells in the liver could not be found. There was even a hypothesis that the hepatocytes themselves retain the ability to divide. Which, however, seemed unlikely, because mature liver cells multiply their own chromosome set: with an increased number of chromosomes, they can synthesize more proteins (which is very important, given the active metabolic work of the liver), but they cannot divide normally – so that each descendant cell gets the correct chromosome set. 

Researchers from the Howard Hughes Medical Institute still managed to detect stem cells in the liver (Source of Liver Stem Cells Identified). Roel Nusse and his laboratory staff monitored how different tissues of living mice respond to molecular signals of Wnt proteins. They are one of the main regulators of cell division, and the fate of stem cells largely depends on them. That is, if we see a reaction to Wnt in some organ, then we have stem cells in front of us. 

When it came to the liver, it turned out that next to its central vein there are clusters of cells that, firstly, have a normal diploid set of chromosomes, and secondly, they actively divide. Their descendants acquire specialized features of mature hepatocytes, multiplying, in particular, the chromosome set. Of course, part of the cells after division remains in the same state in order to maintain the number of the stem group. The Wnt signaling proteins that support cells in the stem state come from the endothelium lining the central vein, that is, in order to turn into a mature hepatocyte, it is enough for the stem cell to move away from the place of origin. (Stem cells behave in a similar way in other tissues.) The results of the experiments are published in Nature (Wang et al., Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver). 

Liver stem cells (red), gradually turning into mature hepatocytes (green).
Photo: Nusse Lab, HHMI at Stanford.

Since we have stem cells on our hands, it means that they can be studied directly. In the near future, researchers want to test how newly discovered cells help the liver heal damage, whether they help to resist diseases such as cirrhosis. On the other hand, it is possible that these stem cells, which suddenly lost control of their own division, can cause liver cancer. 

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17.08.2015