A metabonomics study of Chinese miniature pigs with acute liver failure treated with transplantation of placental mesenchymal stem cells

Abstract

Metabonomics has become a highly sensitive and powerful tool for screening of biomarkers and elucidation of biochemical processes. Recently, we reported beneficial therapeutic effect of human placenta mesenchymal stem cells (hPMSCs) transplantation on d-galactosamine (GalN)-induced liver injury in Chinese miniature pigs. However, the underlying mechanism remains largely unclear. Here, UPLC/TOF/MS-based metabonomics approach was employed to analyze serum from GalN-treated pigs with the goal of identifying potential biomarkers for acute liver injury. Our results showed that obvious metabolic disturbance occurred during acute liver failure (ALF), which can be ameliorated by the hPMSCs transplantation. The metabolic profiles of the hPMSCs transplantation group returned back to the original state 5 weeks after the hPMSCs transplantation. In addition, the result obtained from metabolic trajectory analysis correlated well with those from biochemical analysis and histological examination. Serum levels of several metabolites including glycoursodeoxycholic acid, glycochenodeoxycholic acid, aromatic amino acids, phosphatidylcholine, lysophosphatidylcholine and sphingomyelin, were significantly modified during the process of ALF and cell treatment. Taken together, our study has gained new insight into the molecular mechanism on how hPMSCs administration facilitates the recovery of ALF, and provided strong support for treating liver diseases with stem cell-based therapies.