Abstract
Studies have shown that embryonic stem (ES) cells can be successfully differentiated into liver cells, which offer the potential unlimited cell source for a variety of end-stage liver disease. In our study, in order to induce mouse ES cells to differentiate into hepatocyte-like cells under chemically defined conditions, ES cells were induced by sodium butyrate as inducer for 7 days in the first phase, followed by the combination of hepatocyte growth factor and dexamethasone as inducers for 12 days in the second phase based on an adherent culture system with a two-step induction. The results from the morphology, gene expression, protein molecular markers and cell function of ES-D3 cells derived hepatocyte-like cells demonstrated that mES cells can be differentiated efficiently in vitro to functional hepatocytes under chemically defined conditions, which might be useful as an in vitro system for hepatocyte transplantation therapy and toxicity screening in drug discovery. Key words : Embryonic stem cells, hepatic-like cells, in vitro differentiation, sodium butyrate, hepatocyte growth factor, dexamethason.
Highlights
The liver is the major organ that provides multiple metabolic functions critical for the maintenance of homeostasis
In order to induce mouse embryonic stem (ES) cells to differentiate into hepatocyte-like cells under chemically defined conditions, ES cells were induced by sodium butyrate as inducer for 7 days in the first phase, followed by the combination of hepatocyte growth factor and dexamethasone as inducers for 12 days in the second phase based on an adherent culture system with a two-step induction
Examination with transmission electron microscopy revealed that the Mouse embryonic stem cell (mES) cells derived hepatocyte-like cells were similar to hepatocytes from a morphological viewpoint with abundant microvilli, numerous mitochondria, lipid droplets, rough endoplasmic reticulum, well-developed Golgi apparatus and occluding junctions normally present on the apical domain of hepatocytes (Figure 4)
Summary
The liver is the major organ that provides multiple metabolic functions critical for the maintenance of homeostasis. One of the major causes of morbidity and mortality worldwide is liver failure or end-stage liver diseases for which orthotopic liver transplantation (OLT) is the accepted method of treatment. Transplantation has several limitations, including high cost, side effects for the donor and requirement for immunosuppression, especially, the shortage of organ donors which limit the use of this therapeutic modality. Hepatocyte transplantation therapy provides an alternative therapy strategy for liver failure or end-stage liver diseases (Tanaka et al, 2006). To enhance the potential for this approach, hepatocyte transplantation therapy requires a renewable cell source of functional hepatocytes in vitro. One of the most promising potential sources of functional hepatocytes is from embryonic stem (ES) cell or induced pluripotent stem cells (iPS)
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