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Our understanding of the process of self-renewal has both progressed and changed over the last few decades. For many years, the assumption was that the liver regenerates primarily through the division of hepatocytes. However, over the last few years there has been increasing evidence of the participation of immature cells. Stem cell-fed liver regeneration comprising extensive cell proliferation within the portal areas of the liver lobules occurs when the proliferation of mature hepatocytes is massively impaired, as seen in chronic and severe liver injury. The tissue-determined progenitor cells, termed "oval cells" owing to their predominant morphology, may develop from dormant stem cells located in the canal of Hering. They proliferate and extend into the surrounding parenchyma, differentiating into hepatocytes and bile duct cells. The variable antigen profiles imply that the intrahepatic progenitor cells constitute a dynamic cell compartment, which contains a multitude of cells expressing not only hepatic, but also extrahepatic markers. Selecting one or even several markers to identify and isolate oval cells always determines the choice of target cell. In the search for an alternative source of cells for transplantation purposes, the appropriate stimulus to prepare the host liver for oval cell repopulation as a clinically viable form of treatment remains to be determined. [ABSTRACT FROM AUTHOR]

The severe shortage of deceased donor organs has driven a search for alternative methods of treating liver failure. In this context, cell-based regenerative medicine is emerging as a promising interdisciplinary field of tissue repair and restoration, able to contribute to improving health in a minimally invasive fashion. Several cell types have allowed long-term survival in experimental models of liver injury, but their therapeutic potential in humans should be regarded with deep caution, because few clinical trials are currently available and the number of patients enrolled so far is too small to assess benefits versus risks. This review summarizes the current literature on the physiological role of endogenous stem cells in liver regeneration and on the therapeutic benefits of exogenous stem cell administration with specific emphasis on the potential clinical uses of mesenchymal stem cells. Moreover, critical points that still need clarification, such as the exact identity of the stem-like cell population exerting the beneficial effects, as well as the limitations of stem cell-based therapies, are discussed.

Liver regeneration restores the original functionality of hepatocytes and cholangiocytes in response to injury. It is regulated on several levels, with different cellular populations contributing to this process, eg, hepatocytes, liver precursor cells, intrahepatic stem cells. In response to injury, mature hepatocytes have the capability to proliferate and give rise to new hepatocytes and cholangiocytes. Meanwhile, liver precursor cells (oval cells) have become the most recognized bipotential precursor cells in the damaged liver. They rapidly proliferate, change their cellular composition, and differentiate into hepatocytes and cholangiocytes to compensate for the cellular loss and maintain liver homeostasis. There is a growing body of evidence that oval cells originate from the intrahepatic stem cell(s), which in turn give(s) rise to epithelial, including oval cells, and/or other hepatic cells of nonepithelial origin. Since there is a close relationship between the liver and hematopoiesis, bone marrow derived cells can also contribute to liver regeneration by the fusion of myeloid cells with damaged hepatocytes, or differentiation of mesenchymal stem cells into hepatocyte-like cells. The current review discusses the contribution of different cells to liver regeneration and their characteristics.