Expression of liver‐specific markers in naïve adipose‐derived mesenchymal stem cells

Abstract

Increasing evidence suggests that adipose tissue contains mesenchymal stem cells (MSC) that possess the ability to transdifferentiate into other cell types including hepatocytes, similar to bone marrow-derived stem cells. The existence of precommitted cells in the MSC population may explain transdifferentiation. Our aim was to identify a population of putative hepatocyte-like precursor cells in human adipose tissue. We analysed the 'basal' hepatic potential of undifferentiated, naïve human adipose-derived mesenchymal stem cells (hADMSC). hADMSC were isolated from human adipose tissue and characterized for cell surface markers and for liver-specific gene expression. The isolated undifferentiated naïve hADMSCs expressed MSC surface markers. They also expressed alpha-fetoprotein, CK18, CK19 and HNF4, which are known as early liver expressing genes. Interestingly, the undifferentiated naïve hADMSC were also positive for albumin, G-6-P and alpha-1-antitrypsin (AAT), which are all known to be predominantly expressed in adult liver cells. These cells acquired a hepatocyte-specific phenotype and function upon treatment with a differentiation medium, resulting in the upregulation of albumin, G-6-P and AAT. Moreover, urea production, glycogen storage ability and cellular uptake of indocyanine green, which were absent in the basal state, were evident in the treated cells. Our findings suggest the presence of cells with hepatocyte-like properties that are isolated from human adipose tissue and that can readily acquire hepatocyte-like functions. Adipose tissue could thus be an exciting alternative means for repopulating the liver after various injuries, and might serve as a source for the transplantation of liver cells.