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Received Nov 22, 2017; Accepted Jan 16, 2018
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1. Introduction
Liver fibrosis results from sustained injury, which can be inflicted by various factors such as viruses, drugs, alcohol, metabolic diseases, and autoimmune attacks [1]. Prolonged exposure to these harmful factors causes hepatocyte apoptosis, inflammatory cell recruitment, endothelial cell impairment, and, lastly, activation of hepatic stellate cells, the major cells involved in liver fibrosis. Liver fibrosis is a kind of scar tissue formation in response to liver damage [2–9]. Histologically, it is caused by an imbalance between extracellular matrix synthesis and degradation [10–12].
Liver cirrhosis is a condition where scar tissue replaces the healthy tissue of the liver and regenerative nodules with surrounding fibrous bands develop as a result of the injury [13]. Cirrhosis is the common end of progressive liver disease of various causes, resulting in chronic liver failure entailing complications such as hepatic encephalopathy, spontaneous bacterial peritonitis, ascites, and esophageal varices [14]. Unfortunately, the majority of cases are usually in an irreversible state when diagnosed. Despite current advancements in its management [15, 16], cirrhosis was the 14th leading cause of death worldwide in 2012 [17]. Orthotopic liver transplantation is known to be the only definite solution to end-stage cirrhosis.
However, several problems preclude the prevalent application of the procedure, including immunological rejection and the scarcity of donor sources [18].
In fact, the liver has an inherent regenerative capacity to a substantial degree [19], and, thus, the cessation of those harmful factors may prevent further progression of fibrosis and reverse the situation in some cases [20]. In cases where hepatocyte proliferation is insufficient for recovery from liver injury, bipotent resident liver progenitor cells (LPC) are activated and participate in liver regeneration by differentiating into hepatocytes and biliary epithelial cells [19, 21–23]. However, fibrosis is inevitable when regeneration is exceeded by destruction. Clinical signs of liver failure usually appear after about 80 to 90% of the parenchyma has been destroyed.
Hepatocyte transplantation has been proposed as an alternative approach to transplantation, since hepatocytes have been proven to be strongly associated with liver repair [24–28]. While hepatocyte...