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Stem Cells and Liver Regeneration

Oregon Stem Cell Center, Oregon Health & Science University, Portland, Oregon 97239-3098, USA.
Gastroenterology (Impact Factor: 13.93). 06/2009; 137(2):466-81. DOI: 10.1053/j.gastro.2009.05.044
Source: PubMed

ABSTRACT One of the defining features of the liver is the capacity to maintain a constant size despite injury. Although the precise molecular signals involved in the maintenance of liver size are not completely known, it is clear that the liver delicately balances regeneration with overgrowth. Mammals, for example, can survive surgical removal of up to 75% of the total liver mass. Within 1 week after liver resection, the total number of liver cells is restored. Moreover, liver overgrowth can be induced by a variety of signals, including hepatocyte growth factor or peroxisome proliferators; the liver quickly returns to its normal size when the proliferative signal is removed. The extent to which liver stem cells mediate liver regeneration has been hotly debated. One of the primary reasons for this controversy is the use of multiple definitions for the hepatic stem cell. Definitions for the liver stem cell include the following: (1) cells responsible for normal tissue turnover, (2) cells that give rise to regeneration after partial hepatectomy, (3) cells responsible for progenitor-dependent regeneration, (4) cells that produce hepatocyte and bile duct epithelial phenotypes in vitro, and (5) transplantable liver-repopulating cells. This review will consider liver stem cells in the context of each definition.

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    • "The liver is mainly composed of two epithelial cell types, hepatocytes and ductal cells. Hepatocytes synthesize essential serum proteins, control metabolism, and detoxify a wide variety of endogenous and exogenous molecules (Duncan et al., 2009). Despite their considerable replication capacity in vivo (Michalopoulos, 2014), hepatocytes have resisted long-term expansion in culture (Mitaka, 1998). "
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    • "Liver stem cells (LSCs) have long been favored as the most likely alternative source of hepatocytes in the adult liver. In the classical view, LSCs are nonhepatocyte precursors of highly proliferative progenitor cells that can differentiate into both hepatocytes and biliary epithelial cells (BECs), thereby providing a backup system for liver regeneration (Duncan et al., 2009). In support of this view, cells that are bipotential in vitro can be isolated from the adult mouse liver (Dorrell et al., 2011; Huch et al., 2013; Shin et al., 2011). "
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    • "These multipotent cells are derived from the embryonic cells of the ductal plate. The cells are identified from their expression of progenitor markers: claudin 3, neural cell adhesion molecule (NCAM), or hematopoietic, endothelial, or mesenchymal cell markers , which are not found on hepatoblasts [12]. These cells are located in stem cell niches in the Canals of Hering, anatomically juxtaposed between the intralobular canalicular system of hepatocytes and the biliary tree [29]. "
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