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Abstract
Liver transplantation has been regarded as the definitive curative approach for pathologic liver conditions from the acute stage to the chronic end stage for decades. Recently, translational research has been focused on liver stem cell transplantation, using various cell therapies, due to the potential benefit of natural host liver regeneration. Many studies are ongoing utilizing and evaluating the use of either fetal-liver-derived stem cells or oval cells, however many obstacles still remain. Extensive research identifying and characterizimg stem/progenitor cells for potential application to in vitro cell therapy, whereas many questions remain concerning the isolation and identification of adult liver stem cells with adequate capacity for proliferation and the regeneration of injured liver. Recent approaches to liver regeneration include the production of hepatocyte-like cells from other stem cell sources such as mesenchymal stem cells and embryonic stems cells. Another major target for liver regeneration studies include the generation of liver stem cells from induced pluripotent stem cells (IPSC) We review the current data concerning characterization of stem cells and progenitor cells for their capacity to support their potential for re-population and regeneration of normal adult liver from liver damaged due to injury and/or disease.
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Fig. 1.
Hepatocyte-like cells originate from human MSC. Polygonal hepatocyte like cells stained with PAS indicating glycogen storage were found after three weeks of treatment of cytokine cocktail for human mesenchymal stem cells. Picture image, 200 magnification. MSC, Mesenchymal Stem Cells.
Fig. 2.
Hepatocyte-like cells originate from human pluripotent stem cell. (A) shows morphology of human embryonic stem cell derived hepatocyte like cells (left panel) and expression of albumin as one of the major markers of hepatocytes by immunostaining (right panel). Picture image, 200 magnification. (B) presents hepatocyte like cells (left panel) and albumin expression by immunostaining (right panel) derived from human IPSC after embryoid body formation, endoderm enrichment, and hepatocyte specification protocol for 5 weeks culture period. Picture image, 200 magnification.
Table 1.
Cell types studied in liver regeneration and their characteristics
| Cell | Origin | Properties | Problems |
|---|---|---|---|
| Regenerating hepatocyte [1,2,5] | Adult liver | High host compatibility | Poor proliferation in vitro culture |
| Low availability | |||
| Oval cells [1,2] | Portal areas of adult liver | Bipotency | Hard to isolate |
| Low availability | |||
| Possible tumor formation | |||
| Hepatoblast [2] | Early gestational stage fetal liver | Massive proliferation in vitro culture | Ethical concerns |
| Bipotency in vivo | Low availability | ||
| Fetal hepatocyte [2] | Fetal liver | Easy to isolate | Functional immaturity |
| Multiple proliferation in vitro culture | Low availability | ||
| Ethical concerns | |||
| Possible tumor formation | |||
| Mesenchymal stem cells [1,2,5] | Adult tissue (e.g. bone marrow etc.) | High availability | Transdifferentiation to myofibroblasts |
| No tumor formation | Low hepatic differentiation | ||
| No ethical concerns | |||
| Embryonic stem cells [2] | Embryo | High availability | Ethical concerns |
| Multiple proliferation in vitro culture | Possible tumor formation | ||
| High hepatic differentiation | |||
| Induced pluripotent stem cells [2,2] | Somatic cells (e.g. fibroblast etc.) | No ethical concerns | Possible tumor formation |
| High availability | |||
| Multiple proliferation in vitro culture | |||
| High hepatic differentiation |
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