The liver is structurally and functionally heterogeneous and complex, and it accomplishes crucial functions for the organism. Its most remarkable potential is its capacity to regenerate after injury in order to maintain whole body homeostasis and guarantee the survival of the individual. Under normal conditions, liver regeneration (LR) is attributed to adult hepatocytes, the main cells in the liver which are able to proliferate in response to different stimuli or injuries. Nevertheless, when liver injury is severe and/or hepatocytes are prevented from proliferation, liver stem/progenitor cells (LS/PCs) participate directing LR to maintain liver mass and functions. Different mechanisms have been shown to guide this second line of LR, such as intrahepatic and extrahepatic liver progenitor cells, as well as transdifferentiation processes between hepatocytes and other liver cells. For this reason, many efforts have been made to elucidate the specific molecular mechanisms which orchestrate this process; this in turn would improve the prognosis and treatment of liver diseases. In this review, we revisit the fascinating process of LR, also with a short overview about liver development, the process from which arises the concept of LS/PCs participating in LR, and very important nowadays when considering cell therapy and tissue bioengineering for the treatment of patients suffering from liver disease.
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