Abstract
The replacement of disease hepatocytes and the stimulation of endogenous or exogenous regeneration by human mesenchymal stem cells (MSCs) are promising candidates for liver-directed cell therapy. In this study, we isolated MSCs from adult bone marrow by plastic adhesion and induced differentiation with a liver differentiation protocol. Western blot analyses were used to assess the expression of liver-specific markers. Next, MSC-specific proteins were analyzed with two-dimensional (2D) gel electrophoresis and peptide mass fingerprinting matrix-assisted laser desorption/ionization (MALDI)-time of flight (TOF)-mass spectrometry (MS). To confirm the results from the proteomic study, semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed. We demonstrated that MSCs treated with the liver differentiation protocol expressed significantly more albumin, CK19 and CK20, than did undifferentiated cells. In addition the results of proteomic study demonstrated increases expression of FEM1B, PSMC2 and disulfide-isomerase A3 in MSCs treated with the liver differentiation protocol. These results from proteomic profiling will not only provide insight into the global responses of MSCs to hepatocyte differentiation, but will also lead to in-depth studies on the mechanisms of proteomic changes in MSCs.
Highlights
Most liver diseases lead to hepatocyte dysfunction, with the possibility of eventual organ failure.Previous studies demonstrated the plasticity of mesenchymal stem cells (MSCs) to differentiate into other cells of the mesodermal lineage, including pancreatic cells and hepatocyte-like cells in vitro [1,2,3]
We demonstrated that increases in vimentin, FEM1B, PSMC2 and disulfide-isomerase A3 expression were found in MSCs treated with the liver differentiation protocol
Our findings demonstrate that treating MSCs with the liver differentiation protocol induces a profound change in gene and protein expression that resembled cells derived from hepatocytes from the endoderm
Summary
Most liver diseases lead to hepatocyte dysfunction, with the possibility of eventual organ failure. Previous studies demonstrated the plasticity of MSCs to differentiate into other cells of the mesodermal lineage, including pancreatic cells and hepatocyte-like cells in vitro [1,2,3]. Previous studies have demonstrated that MSCs possess an extensive potential to differentiate into hepatocyte-like cells by using cytokines and growth factors that have a potent effect on hepatic growth and differentiation in vitro [4]. We induced MSCs using a liver differentiation protocol and two-dimensional (2D) electrophoresis to separate the proteins by isoelectric focusing (IEF) and SDS-PAGE. We demonstrated that increased expression of the mesenchymal marker vimentin and FEM1B, PSMC2 and disulfide-isomerase A3 were found in MSCs treated with the liver differentiation protocol
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