Hepatocytes derived from adult stem cells.

UNLABELLED: We characterized the functional properties of mesenchymal stem cells from various human tissues for their potential to differentiate into hepatocyte-like cells in vitro.

METHODS: Mesenchymal stem cells were isolated from human bone marrow (hBM-MSC) and peritoneal and subcutaneous adipose tissues (hpAT-MSC and hsAT-MSC) based on their capacity to adhere to plastic culture surfaces. Cells were analyzed by reverse transcriptase polymerase chain reaction and for urea as well as glycogen synthesis. Their potential for multiple differentiation pathways was investigated by incubation in culture media triggering osteogenic, adipogenic, or hepatogenic features. Global gene expression patterns were analyzed in hepatocyte differentiated hBM-MSC compared with undifferentiated MSC and adult and fetal human liver.

RESULTS: Applying osteogenic or adipogenic differentiation conditions, the cells from each tissue under investigation differentiated appropriately. Treatment of the cells with hepatogenic medium induced mRNA transcripts typical for hepatocytes, as well as the onset of urea synthesis and glycogen storage. Analysis of global gene expression patterns revealed that hepatocytes differentiated from hBM-MSC were clearly distinct from undifferentiated MSC. These cells had acquired features of adult as well as fetal human hepatocytes.

CONCLUSION: In vitro, MSC from human bone marrow and adipose tissue differentiated to hepatocyte-like cells closely related to adult elements on the molecular and functional levels.