Mechanisms of liver regeneration and repair by scarring
THE CONTEXT
The liver regenerates through residual hepatocyte proliferation or stem cell repopulation, with the dominant mechanism determined by the injury.
Hepatocyte proliferation after partial hepatectomy
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In humans, up to 90% of the liver can be regenerated through proliferation of residual hepatocytes.
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Regeneration begins with cytokine priming: IL-6, produced mainly by Kupffer cells, makes hepatocytes competent to receive and respond to growth factor signals.
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Growth factors such as hepatocyte growth factor (HGF) and transforming growth factor alpha (TGF-alpha) then stimulate proliferation of the primed hepatocytes.
Stem cell contribution
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Liver stem cells contribute to repopulation when hepatocyte proliferative capacity is impaired, such as after chronic liver injury or inflammation.
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Some stem cells reside in the canals of Hering, specialized niches where bile canaliculi connect with larger bile ducts.
When repair requires a scar
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When regeneration alone cannot accomplish repair, connective tissue replaces injured cells and forms a scar.
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Scarring can follow severe or chronic injury involving parenchymal cells, epithelia, and the connective tissue framework, or injury to nondividing cells.
Although commonly used for skin wound healing, the term scar also describes collagen replacement of parenchymal cells in other tissues, such as the heart after myocardial infarction.