Differentiation of mesenchymal stem cells (MSCs) to hepatocyte-like cells is associated with morphological and biological changes. In this study, the effect of hepatogenic differentiation on fatty acid profile and the expression of proliferator-activated receptors-α (PPAR-α) have been studied. For this purpose, MSCs isolated from human umbilical cord were differentiated into hepatocyte-like cells on selective culture media. The morphological and biochemical changes, PPAR-α expression and reactive oxygen species (ROS) levels were studied during the differentiation process. Besides, the cells were processed to determine changes in fatty acid profile using gas chromatography analysis. The results showed that hepatic differentiation of the MSCs is associated with a decrease in major polyunsaturated fatty acids in mature hepatocytes, whereas there was an increase in the saturated fatty acid (SFA) levels during hepatocyte maturation. The differentiation-dependent shift in the ratio of SFA/USFA was associated with changes in albumin and PPAR-α expression, whereas changes in fatty acid profile were independent of ROS production and lipid peroxidation in differentiating cells. In conclusion, these data may suggest that hepatocyte formation during the stem cell differentiation is associated with a shift in the fatty acid profile that is probably a normal phenomenon in hepatogenic differentiation of the MSCs.
Resistance to oxidative damages in undifferentiated mesenchymal stem cells (MSCs) in comparison with the undifferentiated progenitor cells may differ depending on several factors. This study was carried out to examine the impact of hepatogenic differentiation process of MSCs on oxidative DNA damage markers. Hepatic differentiation of MSCs was carried out using a two-step conventional protocol and the cells were processed for characterization using morphological and biochemical markers. During the course of differentiation cellular levels of reactive oxygen species (ROS), 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and expression of ataxia-telangiectasia mutated (ATM) protein were estimated at time intervals (10, 20 and 30 days). The results showed a decrease in cellular ROS (13%, P < 0.05) at early stages of hepatogenic differentiation. Similarly, there was a small but significant decrease in 8-OH-dG level and ATM expression in differentiated hepatocytes. Despite the small changes in oxidative damage factors and ATM expression during the differentiation process, the hepatocytes obtained were morphologically and biologically intact.
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