Acute hepatic failure-derived bone marrow mesenchymal stem cells express hepatic progenitor cell genes.

摘要

Hepatic progenitor cell (HPC) transplantation is a promising alternative to liver transplantation for patients with end-stage liver disease. However, the precise origin of HPCs is unclear. This study aimed to determine whether bone marrow mesenchymal stem cells (BMSCs) isolated from rats in acute hepatic failure (AHF) possess hepatic potential and/or characteristics. BMSCs were isolated from normal rats as well as rats in which AHF was induced by D-galactosamine. HPCs and primary hepatocytes were isolated from normal rats for comparison. The Affymetrix GeneChip Rat Genome 230 2.0 Array was used to perform transcriptome profiling of the AHF-derived BMSCs and HPCs. The results showed that AHF-derived BMSCs had a gene expression profile significantly different from that of control BMSCs. More than 87.7% of the genes/probe sets that were upregulated more than 2-fold in AHF-derived BMSCs were expressed by HPCs, including 12 genes involved in liver development, early hepatocyte differentiation and hepatocyte metabolism. Confirmatory quantitative RT-PCR analysis yielded similar results. In addition, 940 probe sets/genes were expressed in both AHF-derived BMSCs and HPCs but were absent in control cells. Compared to the control cells, AHF-derived BMSCs shared more commonly expressed genes with HPCs. AHF-derived BMSCs have a hepatic transcriptional profile and express many of the same genes expressed by HPCs, strongly suggesting that BMSCs may be a resource for hepatocyte regeneration, and further confirming their potential as a strong source of hepatocyte regeneration during severe hepatic damage.